Background: The most frequently cited mediators of reperfusion injury is oxygen free radicals. We hypothesized that acute application of the antioxidants attenuates the reperfusion injury. We investigated the influence of well known antioxidant N-acetyl-cysteine (NAC) and nonspecific cyclooxygenase inhibitor flunixin meglumine, which is often used as MRI dye, in rat ischemia/reperfusion model. Methods and results: In rats, myocardial ischemia was induced by left coronary artery ligation for 30min followed by 120-minite reperfusion. Saline as placebo or flunixin meglumine, NAC was administered intravenously 30min before the onset of coronary ligation. Ischemic myocardium at risk was assessed with Evans blue dye and infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Ischemic myocardium at risk was comparable among groups. Severity of infarction, expressed as a percentage of infarct area in the myocardium at risk, was significantly smaller in NAC treated group (37.4%, placebo 51.5%, p<0.05) and flunixin meglumine treated group(38.3%, placebo 51.5%, p<0.05). Conclusion: These findings suggest that flunixin meglumine as well as NAC reduces myocardial infarct size in rat ischemia/reperfusion model. This is the first study to show in animal model that flunixin meglumine, used for MRI dye, might reduce myocardial reperfusion injury. We propose that flunixin meglumine, MRI dye, could be useful to decrease cardiovascular morbidity and mortality in clinical setting in which oxygen free radicals do major role.