Dietary nitrate, via formation of nitrite and conversion to NO, increases gastric mucosal blood flow and mucus thickness and protects the mucosa against injury. We wanted to investigate if the high levels of NO formed in the stomach after ingestion of nitrate also results in increased intraduodenal NO and how this might affect the duodenal blood flow and NSAID induced inflammation in the duodenum. Rats were given nitrate in the drinking water for 7 days. Intraduodenal NO was measured with chemiluminescence and intestinal blood flow with non-radioactive microspheres in Inactin anesthetized rats. Intestinal inflammation was induced with the NSAID diclofenac. To quantify P-selectin expression in duodenum dual radiolabeled monoclonal antibody technique was used. The adhesion molecule P-selectin plays an essential role in the initial recruitment of leukocytes to the site of injury during inflammation. Dietary nitrate increased intraduodenal NO levels (nitrate pre treated; 707 ± 142 ppb, controls; 11 ± 3 ppb) and increased duodenal blood flow (nitrate pre treated; 3.7 ± 0.4 ml/min, controls; 2.6 ± 0.2 ml/min). Diclofenac caused an up regulation of P-selectin in the duodenum (Diclofenac treated; 2.27 ± 0.35, controls; 1.26 ± 0.12 ng P-sel Ab/g tissue). In the nitrate pretreated animals up regulation of P-selectin was completely prevented (Diclofenac treated; 0.83 ± 0.22, controls; 1.00 ± 0.16). Dietary nitrate increases the duodenal blood flow and potently protects against NSAID induced duodenal inflammation. The protective effects may be related to the increased NO generation in the bowel lumen and an increased blood flow but a cytoprotective effect of circulating nitrite cannot be excluded.