In this study it was of interest to evaluate the impact of nitric oxide (NO) modulation by administration of arginine/NAME, on oxidative stress in experimental colitis induced by 2, 4, 6-trinitrobenzenesulfonic acid. Arginine was used to increase NO levels while NAME lowered oxidant levels. Histopathological findings of colon revealed mucosal inflammation in all groups but significantly higher with arginine alone. The levels of NO and of thiobarbituric acid-reactive substances (TBARS, a marker of lipid peroxidation) were observed to be significantly higher in the arginine-administered group compared to glycine, and these levels were found to decrease on administration of NAME to both glycine- and L-arginine-administered groups. Glutathione peroxidase (GSH-Px) activity and glutathione (GSH) levels were significantly higher in arginine administered group compared to glycine. Significantly higher CuZn superoxide dismutase (CuZn-SOD) activity was observed in the L-arginine + L-NAME group compared to arginine. Data show that NO plays a role in oxidant damage found in experimental colitis and that the use of NAME may potentially inhibit injury.