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Objective: Aqueous root extract of Oroxylum indicum was evaluated in rats against dinitrobenzene sulfonic acid (DNBS) induced colitis. Materials and Methods: Rats were pre-treated orally for seven days and continued for four days after the induction of colitis with OIaq (100, 200, and 400 mg/kg) or vehicle. Colitis was induced by intracolonic instillation of 25 mg of DNBS per rat dissolved in 50% alcohol and 4 days later, the colonic mucosal damage was analyzed along with food intake, body weight, colon weight, spleen weight, histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, reduced glutathione (GSH), and nitric oxide levels in colonic tissue homogenate. Results: Significant reduction in gross damage area, weight loss and increase in colonic and spleen weight were evident in test substance-pretreated animals’ dose dependently as compared to vehicle treated control. These effects were confirmed biochemically by a reduction in colonic myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and increase in reduced glutathione (GSH) levels. Furthermore, microscopic examination revealed diminution of inflammatory cell infiltration and submucosal edema in colon segments of rats treated with OIaq. Conclusion: The results demonstrate the protective effect of OIaq in the animal model of acute colitis possibly through an antioxidant, anti-lipoperoxidative or due to reduction in nitric oxide generation.