Since oleic acid (OA) induces morphologic and cellular changes similar to those observed in human acute lung injury (ALI) and acute respiratory distress syndrome, it has become a widely used model to investigate the effects of several agents on pathogenesis of lung injury. The antioxidant and anti-inflammatory properties of N-acetylcysteine (NAC) has been documented in many lung injury models. In this study, we evaluated the role of NAC in an OA-induced lung injury model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in lung tissue. Five groups labelled Sham, NAC, OA, Pre-OA-NAC and Post-OA-NAC were determined. ALI was induced by intravenous administration of OA. The pre-OA-NAC group received iv NAC 15 min before OA infusion and the post-OA-NAC group received iv NAC 2 h after OA infusion. In both of the NAC treatment groups' blood and tissue samples were collected 4 h after OA infusion, independent from the time of NAC infusion. The MPO activity, MDA and 3-NT levels in lung homogenates were found to be increased in OA group and the administration of NAC significantly reduced tissue MPO, MDA and 3-NT levels (p = 0.0001) Lung histopathology was also affected by NAC in this OA-induced experimental lung injury model.