Objectives: This study was carried out to explore the possible anti-inflammatory effect of ibudilast on acetic acid-induced colitis in rats. Methods: Fifty adult Wistar rats were separated into 5 groups, including the control group, acetic acid group, acetic acid + vehicle, acetic acid + sulfasalazine (100 mg/kg/day)group, and acetic acid + ibudilast (30 mg/kg/day) group. Colitis was induced in rats by the inter-rectal installation of 2 ml of 4% (v/v) acetic acid. Sulfasalazine and ibudilast were administered orally for ten days after 2 hours of induction. Results: The treatment with ibudilast significantly reduced disease activity index (DAI), macroscopic colonic scores (MAC), and histopathological changes induced by acetic acid. Also, ibudilast markedly decreased the expression of proinflammatory markers (TNF-α and IL-1β) in colonic tissue. Moreover, ibudilast inhibited myeloperoxidase (MPO) enzyme activity that was increased by acetic acid. Conclusion: Therefore, ibudilast may have a therapeutic effect in the management of ulcerative colitis.