A docking analysis performed on four selected imidazo[1,2-a]pyridine carboxylic acid derivatives indicated the binding of these to enzymes COX-1 and COX-2 active pockets. An in vitro analysis showed that compound 3-amino imidazo[1,2-a]pyridine-2-carboxylic acid (5) preferentially inhibited COX-2. The compounds (10 mg/kg) were evaluated in relation to a potential acute and chronic anti-inflammatory activity. Compound (5) and imidazo[1,2-a]pyridine-2-carboxylic acid (2) inhibited the edema produced by carrageenan more efficiently than indomethacin. Chronic anti-inflammatory activity was found in derivative (5) and indomethacin-treated groups in the granuloma model, the compound (2) and nitro-acid (4) had only a fair activity. Compound (2), nitro-carboxylate (3), and (5) did not produce gastroduodenal damage.