Mesenteric ischemia is a devastating disease process that frequently challenges clinicians. To enhance the early diagnosis of gut ischemia and judgment of its severity, it may be helpful to detect the unusual existence or increase in biomarkers in the body fluid. The aim of the present study was to evaluate the correlation of plasma nitric oxide (NO) and endothelin-1 (ET-1) levels to mesenteric ischemia using an animal model. Acute mesenteric ischemia (AMI) was produced experimentally by occlusion of the mesenteric vessels in the terminal ileum by the tenting of a thread. The determination of plasma NO and ET-1 levels were obtained before operation (T0, baseline value), and at 10 (T10), 20 (T20), 30 (T30), and 60 (T60) min after the creation of AMI. Sham-operated rats served as controls. After 30 min of experiments, the plasma NO and ET-1 levels were significantly higher in the AMI group than in the control group (both p < .01). Both the plasma NO and ET-1 levels in AMI group increased significantly after 30 min of ischemia (both p < .001 vs. respective baseline value), and they were 60% and 84% above the baseline value, respectively. In addition, ischemic intestinal injury was confirmed by the significantly elevated histological scores in the AMI group after 60 min of ischemia (p < .001). Our preliminary results suggest the possibility of important insights regarding NO and ET-1 changes into the mechanism of pathogenesis in AMI in rats. The increases in plasma NO and ET-1 levels may potentially be noninvasive biomarkers for the early detection of this disease.