When the country's independence was declared in 1844, De Regla had already managed to develop a successful military career and served as colonel of the National Militias.

Once the First Dominican Republic was proclaimed, the separatist movement commissioned him to lead the first contingent of troops in the cities of Baní and San Cristóbal with the mission of defending the border line of the island.

When Santana resigned as head of State on 26 May 1856, De Regla assumed the presidential position although, a few months later, the strong pressure he received from the Spanish government forced him to leave the National Palace and leave power in the hands of Buenaventura Báez, the eternal political enemy of the "Santanistas".

De Regla accompanied his friend in exile until both were able to return to the country after the outbreak of the revolution of July 1857.

Fearing a new Haitian invasion, Santana proclaimed annexation to Spain in 1861 and, in a new show of loyalty to his protector and friend, De Regla supported the decision of his political superior.