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, aqueous and methanolic extracts of Holarrhena antidysenterica were tested for 2, 4 - dinitro benzene sulfonic acid (DNBS) induced colitis, and antioxidant activity were evaluated to clarify possible mode of action. Male albino wistar rats were randomly divided into six 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), colitis treated with aqueous extract of test drug Holarrhena antidysenterica (Group VI). 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, V & VI as compared to those of Group III. There was also increase in food intake, water intake & decreased colon weight in Group IV, V & VI 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, V & VI as compared to those of group III. Levels of all the chemical parameters, Physical parameters & Histological parameters were significantly improved after the treatment with methanolic extract of test drug compared to aqueous extract of test drug. Treatment with aqueous extract also improves the colitis condition but it was not significantly improved by it as compared to methanolic extract of test drug. The results of our study suggest that therapy with methanolic extract of Holarrhena antidysenterica has beneficial effects on the course of experimental colitis compared to aqueous extract of Holarrhena antidysenterica.