||Inflammatory bowel disease (IBD) (ulcerative colitis and Crohn’s disease) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract.The present study was carried out to evaluate the effect of ethanolic extract of Nigella sativa in experimentally induced inflammatory bowel disease (IBD) in rats. Colitis was induced by a single intra-colonic application of 20 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 35% ethanol into the descending colon. Rats were divided into six groups. Animals were treated with vehicle (ethanol), TNBS dissolved in 35% ethanol, Ethanolic extract of Nigella sativa seeds (ENS) 100, 200 and 400 mg/kg body weight p.o. and sulfasalazine(SSZ) 360 mg/kg body weight p.o. for 14 days. After completion of 14 days of treatment, animals were sacrificed and the following parameters were assessed morphological score, histopathology and biochemical parameters like myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) activity and serum nitrate levels. Nigella sativa provided protection against TNBS-induced colonic damage. There was significant protection with ENS 200 and 400 mg/kg body weight compared to control (P <0.001). Morphological and histological score were significantly reduced in all the treated groups (P<0.001). All parameters were altered in ulcerated rats, and improved in animals receiving ENS, an effect that was comparable to that of the standard sulfasalazine, especially at the highest dose level. Results indicate efficacy of ENS against TNBS induced experimental colitis in rats.