Purpose: Acute mesenteric occlusion is a serious clinical entity which usually requires prompt surgical intervention. Although reperfusion is mandatory for the repair, the release of free oxygen radicals and the induction of neutrophyl accumulation attenuates the injury. NFkappa B has a critical role in inflammatory process. This study is based on the hypothesis that sulfasalazine, a potent inhibitor of NF-kappa B may counteract or decrease the ischemia/reperfusion (1/R) injury in rats. Materials and Methods: The study consisted of three groups each containing 10 rats. In the control group (Group I) superior mesenteric artery was dissected, but not ligated. Two hours later tissue samples from ileum and blood samples from portal vein were taken and the rats were sacrificed. In I/R group (Group II) after dissection of superior mesenteric artery, it was clamped just distal to the origin from aorta. Clamp is released after 1 hour ischemia and tissues were reperfused. The same samples as in control group were taken. In sulfasalazin group (Group III), apart from group II. 30 minutes after the beginning of the ischemia, sulfasalazine was given. The tissue samples from ileum were stained for iNOS, p65 and caspase immunohistochemically. NO level was determined in blood samples by Greiss reaction. iNOS, p65 and caspase protein expressions in tissue sections and NO levels in serum were at the basal level in control group. Results: In I/R group both protein expressions and serum NO levels were very high. However in sulfasalazine group, these parameter levels were found higher than control group, but less than the levels found in I/R group. Statistical analysis showed that although there was significant difference between control group and I/R group (p<0.05) with regard to serum NO levels, iNOS and caspase expressions, sulfasalazin group has no significant difference when compared with control group (p>0.05). p65 expression was found to be significantly increased in I/R group compared to control group (p<0.05), whereas in sulfasalazine given group the expression decreased compared to I/R group. However, the decrement was not statistically significant. Conclusion: This study demonstrated that sulfasalazin may have protective effect on experimental rat intestinal ischemia-reperfusion injury through down-regulation of tissue proteins responsible from celluler damage.