Meksi was a member of the "Filiki Etaireia", a secret society whose purpose was to overthrow Ottoman rule over the Balkans and to establish an independent Greek state. When the Greek War of Independence broke out in 1821, after his translation had been completed, Meksi joined the Greeks in the Siege of Tripolitsa. Despite suffering from a serious bout of pneumonia, he continued to work as a physician during the war. He is also said to have taken part in the negotiations leading to an agreement proposed by Theodoros Kolokotronis that permitted the Albanians who were defending Tripolitsa to leave unharmed, an arrangement that helped the Greeks to capture the town from the Turks.