ABSTRACT : Introduction: Diversion colitis (DC) is a benign condition characterized by the appearance of inflammation in the mucosa of the colon or rectum devoid of fecal stream. Oxidative stress has been associated with the etiopathogenesis of the disease. N-acetylcysteine (NAC) is a substance with antioxidant properties, used in different treatments of inflammatory diseases. The purpose of this study was to evalu-ate the effects of topical applications of NAC in an experimental model of DC. Methods: Thirty-six Wistar rats were submitted to deviation of fecal stream by proximal colostomy and a distal mucosal fistula. They were distributed into 3 experimental groups of 12 animals accord-ing to the daily application of enemas containing 0.9% saline or 2 doses of NAC, 25 mg/kg and 100 mg/kg, respectively. In each group, half of the animals were sacrificed after two weeks of irrigation and half after four weeks of irrigation. The diagnosis of colitis was assessed by histopathological analysis and the grade of inflammation by inflammatory grading scale. The results were evaluated with the Mann-Whitney test, adopting significance level of 5% (p<0.05).