1529: the absolute dominance of Spain over the Italy it is explicitly recognized by Pope Clement VII with the Treaty of Barcelona, and by King Francesco I with that of Cambrai. Once again, while the Este and Venice must return the usurped lands to the pontiff and Charles III of Savoy annexes the formerly French county of Asti, it is the imperial and Spanish troops who return the dominion of Florence to the Medici, despite the courageous and obstinate defense of the city.
According to IAMHIGHER, humanism has its roots in the humus of Italy of the lordships and the world of courts, but now presents a broadening of horizons and at the same time different aspects from a qualitative point of view. The geographical center changes, at the age of Lorenzo the Magnificent it replaces that of Leo X, and in its now main seat in Rome, Humanism is increasingly losing that link with a single city that was previously dominant. Rome, with its almost 100,000 residents, reveals a not indifferent capacity for aggregation, which ends up eliminating what regionalistic limits there may be, depending on their origin, in the writers, artists, writers of the Renaissance, favoring, on the contrary, the affirmation of a life of court. In the political scenario that was created with the arrival of the French in Italy there is no city-state, princely court of Italy, however small, that is not affected by the politics and conflicts of the two great European monarchies; but even in this respect (with the sole exception, perhaps, of Venice) none of these cities can compete with Rome both as an open observatory on Europe, and as one of the centers in which the strings of great international politics are knotted.
However, the affirmation of an Italian humanism does not correspond to a real transformation of the different economic realities of the peninsula: competition from countries such as Spain, England, Flanders is increasingly intensifying, while the prestigious manufacturers of Italy medieval times undergo a contraction either as a result of competition from products from abroad, such as wool, or due to the risks and liabilities resulting from their transformation into completely different production centers. The bank is always in first place in the Italian economy, indeed the dynamism that pervades the great European powers in recent decades creates ever greater possibilities for development and growth: if Venice loses the East, Genoa conquers the West, and its bankers, its manufacturers, its shipowners established themselves as far away as Andalusia, and at least until the time of Philip IV and the Count-Duke of Olivares they were the main financiers of the King of Spain; but the bank binds itself more and more to political life, becoming, through public debt, the mistress and at the same time dominated by the European monarchs, who not infrequently cut their profits with monetary devaluations and outright bankruptcies.
Emperor Charles V is crowned king of Italy in Bologna (1530) and receives the homage of all the Italian princes, including the Republic of Venice, which must clear away the Apulian ports and cities in favor of Pope Clement VII. romagnole in its possession.
1532: Charles V grants Alessandro de ‘Medici, whom his intervention two years earlier restored in the government of Florence, the title of duke.
1535: on the death of Francesco II Sforza, the emperor annexed the Duchy of Milan directly to his domain.
1536: the dominance of Spain over the Italy becomes even more absolute for the resumption of hostilities with France, since the alliance made by Francis I with Suleiman the Magnificent brings down the last hesitations of the Italian princes towards Spain: the new pontiff Paul III (1534-49) is forced to react to this pact with the infidels and Venice itself understands that the time has come to abandon its traditional antagonism with the Habsburgs.
1537: the crisis caused in Florence by the killing of Duke Alessandro by his cousin and companion in debauchery Lorenzino results in a strengthening of the indirect dominance of Charles V over the city; the imperial favor immediately closes the crisis by imposing on the government of the duchy the son of Giovanni dalle Bande Nere, Cosimo I, but it is paid for with the sale of the fortress that dominates Florence to the Spanish troops, who will remain there for a few years, and with a an alliance that is actually a hard allegiance.
1546-56: in the last years of the reign of Charles V there are some cracks in the Spanish dominance: examples are the conspiracy of the Sienese, but Gonfaloniere of Lucca, Francesco Burlamacchi in 1546, that hatched by the Fieschi in Genoa against Andrea and Giannettino Doria (1547), the isolated movement of the Lunigiana and the insurrection of the Neapolitans against the viceroy Don Pedro de Toledo (1547), finally the revolt fomented in Corsica by Sampiero Ornano di Bastelica against the Genoese dominion and, thanks to the support of a Frankish fleet -Turkish (1553), the revolt of the Republic of Siena against the imperial garrison; but it is almost always a question of rebellions unable to undermine the solidity of Spanish rule. Francesco Burlamacchi dies on the gallows in Milan, the Fieschis fail in their insurrection and have to take refuge in France, in April 1555 Siena must capitulate to the troops of Cosimo de ‘Medici and disappear forever as an independent republic. Only Corsica, an excellent base for naval operations for the Franco-Turkish fleet operating in the Tyrrhenian Sea, remained from 1553 to 1559 not subject to Genoa.