The carrageenan-induced-air pouch is a particularly good model for evaluating the relationship between inflammation and its related vital mediators. Vildagliptin is an active dipeptidyl peptidase-4 (DPP-4) inhibitor, which is known to possess an anti-hyperglycemic efficacy. The present study was established to investigate the effect of vildagliptin on the carrageenan-induced air pouch model of inflammation. Four groups of rats, each containing eight rats, were used. The experiment was performed over six days. Starting from the first day of the experiment, an air pouch was established on alternate days in the four groups by injecting 20 ml of sterile air subcutaneously into the rat intracapsular area. On the last day of the experiment, rats in the third and fourth groups received vildagliptin 5, and 10 mg/kg, respectively, orally half an hour before carrageenan was given. The second group received indomethacin (10 mg/kg) half an hour before carrageenan was given. Three hours later, the air pouch was opened and the entire exudate of each animal was harvested to assess myeloperoxidase (MPO) & superoxide dismutase (SOD) activities, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-ᴋB), cyclooxygenase 2(COX-2), prostaglandin F2-alpha (PGF-2α), interleukin 10 (IL-10) levels. Vildagliptin 5 mg/kg, 10 mg/Kg, and indomethacin significantly suppressed the NF-ᴋB signaling pathway, reduced TNF-α, MPO, COX-2, PGF2-α levels, while enhancing that of IL-10, and SOD activity. The findings of this study revealed that vildagliptin has an inhibitory effect on inflammation in carrageenan-mediated air pouch in rats by inhibiting COX-2/PGF2-α activity and suppressing the NF-kB signaling pathway.