Background: N-acetylcysteine ​​(NAC), as an antioxidant, has been proven to have protective effects on cells undergoing oxidative stress. In the case of skeletal muscles, NAC can reduce muscle fatigue by decreasing Na⁺ K⁺ pump activity during exercise, and improve skeletal muscle microcirculation in an experimental model of severe closed soft-tissue injury. Purpose: This study aims to determine NAC effects on the ischemia-reperfusion injury of skeletal muscles by measuring tissue malondialdehyde (MDA) levels and edema, as well as the effect of NAC dose on MDA levels. Method: Randomization was carried out to 30 white rats (Rattus norvegicus), which then divided into 3 treatment groups, i.e., K group as the control group (NaCl 0.9%), PTX (Pentoxyfilline) group, as well as P1, P2, and P3 treatment groups. ANOVA test was employed to identify the differences in MDA levels and water content among groups. Results: ANOVA test results indicated that there was a significant difference between the control group (K) and the treatment group given NAC (P1, 2, 3), p = 0.007, while there was no difference in edema indicating that there were no different data groups among the five treatment groups with a p-value = 0.616 (p> 0.05). Conclusion: NAC administration provides positive results by reducing tissue MDA levels with the recommended dose of 200 mg/kg of body weight. NAC administration does not reduce tissue edema, and there are no significant differences with the Pentoxifylline group.

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