Skeletal muscle ischemia reperfusion injuries can occur with diseases, trauma and during surgical procedures. Ischemia reperfusion injury is characterized by the production of oxygen free radicals leading to disturbances in vasomotility and microvascular permeability. The objective was to evaluate effects of N-acetylcysteine as a scavenger of radical oxygen species on the serum enzyme changes secondary to muscle ischemia reperfusion. Twenty wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I) and group ischemia-reperfusion + N-acetylcysteine (group II). After ketamine (50 mgkg-1) and xylazine (10 mgkg-1) anesthesia, femoral artery was exposed and undergone 2h of ischemia, 24h of reperfusion. Rats that were treated with N-acetylcysteine given intravenously at a dose of 150 mgkg-1, immediately before reperfusion. After 24h of reperfusion, the blood samples were collected and submitted for evaluation of serum aspirate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehrdrogenase (LDH) values to identify the ischemic damage occurring in the skeletal muscle tissue. Enzymatic parameters (CPK, AST, ALT and LDH) measured for demonstrating ischemia induced muscle injuries were lower in the group receiving Nacetylcysteine. In this study, N-acetylcysteine as an antioxidant substance was demonstrated to have protective effects on acute ischemia and reperfusion injury of the skeletal muscle in lower extremities.