Inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) play an important role in the pathology of ischemia-reperfusion. This study sought to determine if the pro-inflammatory effects of complement modulate iNOS and SOD in the rat following gastrointestinal ischemia and reperfusion (GI/R). An inhibitory or non-inhibitory anti-C5 monoclonal antibody (18A and 16C, respectively) was administered prior GI/R. RT-PCR revealed a significant increase in intestinal iNOS mRNA compared to sham following GI/R that was significantly attenuated by 18A. Immunohistochemistry demonstrated increased iNOS protein expression within the intestinal crypts following GI/R. Cu/Zn SOD (mRNA and protein) were unaffected by GI/R, whereas Cu/Zn SOD activity was significantly reduced. Mn SOD protein expression was significantly decreased by GI/R. Anti-C5 preserved Cu/Zn SOD activity and Mn SOD protein expression. Staining for nitrotyrosine showed that anti-C5 treatment reduced protein nitration in the reperfused intestine. Immunohistochemistry demonstrated prominent phosphorylated (p)-IB- staining of intestinal tissue after GI/R, while anti-C5 reduced p-IB- expression. These data indicate that complement may mediate tissue damage during GI/R by increasing intestinal iNOS and decreasing the activity and protein levels of Cu/Zn SOD and Mn SOD, respectively.