Hyperbaric oxygen (HBO) treatment reduces ischemia reperfusion injuries via nitric oxide synthase (NOS) and vascular endothelial growth factor (VEGF). The purpose of this study was to determine the effects of ischemia and HBO on VEGF plasma concentrations. As well as, the activity of NOS in the ischemic muscle and the abdominal aorta since HBO works systemically. The anterior gracilis muscle was raised (isolated) in 40 male Wistar rats and randomly assigned to four groups: 1) nonischemic control (Sham), 2) ischemia reperfusion (IR), 3) IR treated with HBO (IR-HBO), and 4) nonischemic control treated with HBO (Sham-HBO). Ischemia was induced by clamping the femoral artery for four hours; the clamp was removed for reperfusion. HBO treatment consisted of 100% oxygen at 2.5 atmospheres for the last 90 minutes of ischemia. Plasma and tissue were harvested after 30 minutes of reperfusion. Those tissues harvested were the anterior gracilis muscle and the abdominal aorta. The plasma VEGF concentrations were determined via ELISA, and the activity of both endothelial NOS (eNOS) and inducible NOS (iNOS) were determined by using [H3] arginine. Group comparisons were made by ANOVA with mean differences compared by Duncan#'s post-hoc analysis. A p > 0.05 was accepted as significant. Data is presented as mean ± SEM. The results for the plasma VEGF levels indicated that ischemia and HBO caused a significant decrease in plasma concentrations of VEGF, and the NOS activity levels implied there were significant increases in eNOS activity due to HBO treatment in this model. Given this information it is probable that a decreased amount of VEGF is seen in the plasma following ischemia and HBO because VEGF is binding to the endothelium and becoming more active. VEGF when activated leads to the downstream activation of eNOS, which can be seen in the increased activity of eNOS following HBO treatment.