Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to antidepressants with serotonin norepinephrine reuptake inhibition property. The anti-inflammatory effect of venlafaxine has been studied in different studies and different models including animals and humans. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine on ulcerative colitis model in rats. We examined the anti-inflammatory effects of venlafaxine in the rat model of acetic acid induced colitis. Colitis was induced in rats by intra rectal injection of 2ml acetic acid 4%. After induction of colitis there were six groups; group1control, group 2 actic acid, group 3 dexamethasone, groups 4,5 and 6 treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic assessment, pathological examination and myeloperoxidase activity measurements. Results showed that, after induction of colitis acetic acid group showed sever inflammation, ulceration, bleeding and necrosis, while venlafaxine at doses of 20 and 40 mg/kg as well as dexamethasone significantly improved colitis parameters in colonic tissue of animals. Compared to acetic acid and control, venlafaxine reduced signs of inflammation; it lowerd elevated myeloperoxidase and improved pathological picture both micro and macro in this animal model of induced colitis. Venlafaxine was found to have anti-inflammatory activity in the animal model of ulcerative colitis, as it decreased myeloperoxidase level and improved the histo-pathological profile in the colonic tissue of rats.