It has been demonstrated that Holarrhena antidysenterica Wall. (Apocynaceae) is useful as an adjunctive therapy for Inflammatory bowel disease (IBD). However, its effect on ulcerative colitis has not been investigated. In the present study, Holarrhena antidysenterica was tested for 2, 4 - dinitro benzene sulfonic acid (DNBS) induced colitis, and antioxidant activity was evaluated to clarify its possible mode of action. Male albino wistar rats were randomly divided into five groups: Normal control (Group I), Vehical contol (Group II), colitis induced by DNBS without any therapy (Group III), colitis treated with standard Dexamethasone (Group IV), colitis treated with methanolic extract of test drug Holarrhena antidysenterica (Group V). Treatment was given for 18 days. Rats were sacrificed on the 18th day after the procedure and the levels of Malondialdehyde (MDA), Nitric oxide (NO), Reduced gluthathione (GSH), Superoxide dismutase (SOD) were measured in the isolated colon tissue. MDA & NO levels in colon tissue homogenate were decreased while SOD & GSH level were increased in group IV & Group V as compare to those of Group III. There was also increase in food intake, water intake & decreased colon weight in Group IV & Group V as compared to Group III. There was also improvement in inflammatory indices of colon mucosal damage index (CMDI) & disease activity index (DAI) & histopathology of Group IV & Group V as compared to those of group III. The results of our study suggest that Holarrhena antidysenterica therapy has beneficial effects on the course of experimental colitis.