"The consulate in Bitola, a town of a rich past and great people, will help to bring closer the Croatian and Macedonian people, who face the same goal of joining the European Union," Mesic said at the opening ceremony.
He added that EU membership would provide the two countries with "security and capital, but first they have to do their job."
Mesic was the first foreign head of state to visit the town, which Mayor Vladimir Tulevski described as a great event.
Speaking at the end of his two-day visit, Mesic said that the visit, which also included a 40-strong Croatian business delegation, was very successful for both the Croatian and the Macedonian side.
Croatia is the seventh country to open a consulate in this town with a rich consular tradition dating from Ottoman times when all big powers had their diplomatic missions there. The tradition is now being revived, with France and Turkey being the first to open their honorary consulates in the town.