Objective Regional circulatory changes in intestinal mucosa were evaluated after the onset of septic shock and the effect of nitric oxide (NO) inhibition on mucosal blood Row was investigated at different locations along the intestine. Summary Background Data: The response of intestinal blood flow to different physiologic and pharmacologic stimuli is known to vary along the intestine, but limited data are available on regional alterations in intestinal blood flow during septic shock. These regional variations in intestinal blood flow could become important because NO inhibition might restore the circulation of one segment of the gut or exacerbate ischemia that may be occurring Concomitantly in another segment of the intestine. Methods Mucosal blood flow was studied with fluorescent microspheres in conscious unrestrained rats before and 2, 4, and 6 hours after lipopolysaccharide (IFS, 20 mg/kg intraperitoneally)induced sepsis in the presence and absence of the nitric oxide synthase inhibitor N-3-nitro-L-argininemethylester (L-NAME, 5 mg/kg subcutaneously). Results Control mucosal blood flow was significantly higher in the ileum than in the duodenum, jejunum, or colon. During LPS-induced sepsis, mucosal blood flow to the ileum decreased and perfusion to the remaining gut was preserved. This was accompanied by hypotension throughout the experiment. L-NAME administration during sepsis prevented hypotension and decreased mucosal blood flow to all segments of small intestine at 2 hours; In this group, mucosal blood flow to the proximal small intestine but not to the ileum returned to baseline levels at 4 and 6 hours. L-NAME alone decreased mucosal blood flow to the small intestine throughout the experiment. Conclusions: This study indicates that mucosal blood flow alterations during septic shock vary along the intestine, with a significant change only in the ileum, suggesting that perfusion in the small intestine is dependent on physiologic NO production.