Nitric oxide (NO) production is increased in the intestine and may contribute to intestinal injury in sepsis. However, the tissue expression of inducible NO synthase (iNOS) mRNA throughout the digestive tract and its relation with the mucosal damage after endotoxin challenge remain unknown. We therefore measured tissue expression of mRNA encoding iNOS by Northern blot analysis and reverse transcription PCR. The iNOS mRNA was detectable at 1 h, peaked at 4 h, and remained faint at 24 h after endotoxin injection in esophagus, duodenum, jejunum, ileum, and colon, but not in the stomach. Pre-treatment with dexamethasone attenuated the rise of iNOS mRNA. Both dexamethasone and NOS inhibitor, L-NAME, ameliorated the endotoxin-induced increase in intestinal mucosal permeability. Our results indicate that there is tissue-specific expression of iNOS mRNA in the digestive tract. The manipulations that decrease NO production may have therapeutic potential in preserving intestinal mucosal integrity in sepsis.