Background: Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, exists as two isoforms, cyclooxygenase-1 and cyclooxygenase-2. Previous studies have shown the protective effect of cyclooxygenase enzyme in the development of convulsion. However, the involvement of Cyclooxygenase-1 in the pathogenesis of epilepsy has not well known. The present study was designed to explore whether indomethacin (a nonspecific COX inhibitor) can affect pentylenetetrazole (PTZ)-induced kindling in rats.Materials and Methods: Kindling, as a chronic model of epilepsy, was inducted by the intraperitoneal injection of PTZ (37.5 mg/kg) every 48 hours (13 times) in all groups. In the pre-treatment groups, intraperitoneal injection of indomethacin (2.5, 5, 10 mg/kg) was done 20 min before each PTZ injection. In sham group, tween (20%) was used as a solvent.Results: Repeated injections of PTZ after 13 sessions significantly induced the kindling in the control group. In pre-treatment groups, indomethacin (2.5, 5, 10 mg/kg) significantly decreased PTZ-induced mean kindling scores.Conclusion: The finding that the indomethacin can partially reverse the kindling mean scores in rat indicates the involvement of CYCLOOGYGENASE-1 isoform. It seems that CYCLOOGYGENASE-1 inhibitors could be a useful choice for the treatment of epilepsy.