Ischemia and reperfusion of skeletal muscle occurs in acute vascular occlusion and revascularization, in elective vascular surgery, in upper and lower extremity surgery by means of a tourniquet, and in free transplantation of muscle containing cutaneous flaps. During revascularization of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids are released that may have a role in the pathogenesis of reperfusion injury. The exact role of eicosanoids in the imposed ischemia-reperfusion induced functional deficits in skeletal muscle is still unknown, we compared tissue edema and the changes of eicosanoids and the effects of cyclooxygenase inhibitor indomethacin in the rat right hindlimb by application of tourniquet ischemia-reperfusionn injury. After 4-hours of ischemia, reperfusion was established 4 hours by releasing tourniquet. Experimental groups comparised ischemia-reperfused animals pretreated with indomethacin 20 mg/kg. The control animals received normal saline, 4 hours of ischemia without reperfusion. To assess tissue edema, wet/dry weight ratios were determined and the concentrations of prostaglandins and thromboxane were measured by the high performance liquid chromatography with UV detector at 195 nm. Ischemia itself did not result in muscle edema and did not increase the release of cyclooxygenase metabolites, but muscle edema(52%, p<0.01), and the relase of 6-keto-PGFalpha(151%, p<0.01), thromboxane B2(98%, p<0.05), and PGE2(127%, p<0.01) were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema(35%, p<0.05 versus ischemis-reperfusion control) and decreased 6-keto-PGF1alpha(65%, p<0.05) releases. These results support view that cyclooxygenase products may play significant roles in the formation of ischemic muscle edema and suggest that nonsteroidal antiinflammatory agents and eicosanoids antagonists might be beneficial to the management of acute limb ischemia-reperfusion injury.