The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on indomethacin-induced small intestinal injury in rats. Single administration of indomethacin provoked severe inflammatory lesions in the small intestine. The levels of thiobarbituric acid-reactive substances (TBARS), myeloperoxidase (MPO) activities and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in the indomethacin-treated group compared with the sham group. In addition, the angiotensin II type I receptor was increased in the small intestine after the administration of indomethacin. The development of intestinal lesions in response to indomethacin was prevented by pretreatment with CV-11974 together with significant suppression of the increased level of TBARS, MPO activities and CINC-1. These results indicate that CV-11974 protected against the small intestinal damage elicited by indomethacin, which suggests that angiotensin II/AT1 receptor interaction is involved in the pathogenesis of the intestinal inflammation associated with oxidative stress.