Under the government of Juan Manuel de Rosas, he had to leave the country, as his liberal ideas did not please the dictator at all. From his refuge in Montevideo, he supported the opposition against de Rosas, both financially and through publications.
When Rosas was deposed by Justo José de Urquiza, Alsina returned to Buenos Aires, and he was elected provincial Governor in 1852. However, he resigned after a few months, shortly before a military coup took place. In 1853, Buenos Aires left the Argentine Confederation and declared itself an independent state. Alsina, a fervent supporter of Buenos Aires Province independence, became Governor again in 1857. In 1859, open hostilities broke out between Buenos Aires and the Argentine Confederation, led by Urquiza. After the defeat of the Buenos Aires army at the Battle of Cepeda on October 23, 1859, Alsina had to resign his post, and shortly after Buenos Aires rejoined the Confederation. Alsina became a member of the Argentine Senate in 1862.
