Background: Hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors (statin) have been shown to reduce atherosclerotic cardiovascular mortality and morbidity. Recent evidence indicates that statin exert direct beneficial effects on vascular cells that are independents of lipid-lowering effects. However, very little is known about whether statin have direct effects on myocardium. Methods: To test the effects of hydrophilic and lipophilic statins (pravastatin and atorvastatin) in cardiac ischemia-reperfusion (IR, 30 minutes left anterior descending artery ligation and 24 hours reperfusion) injury, 10 mg/kg of drugs were given in Sprague-Dawley rats weighing 250-300 g with standard chow diet one week before IR injury and thereafter. To profile gene expression patterns involved statin treatment and IRI injury, we monitored gobal gene expression changes by cDNA microarray analysis of rats-specific genes. Results: The ischemic area was not affected by statin treatment. Both statins reduce infarction (%MI) compared with control group (p<0.01 in atorvastatin and p<0.05 in pravastatin, n=8 in each). The number of infiltrated polymorpho neutrophils and myeloperoxidase activity in the ischemia area were decreased compared with control group (p<0.05, n=5 in each). Statin treated group did not increase IR-induced apoptosis (DNA laddering, n=5 in each). Genes with apoptosis and cell death in statin treated group were not altered significantly compared with control group. Conclusions: Thus, lipophilic and hydrophilic statin could prevent IR injury via decreased inflammation. The pro-apoptotic effect of statin was not observed in IR injury rat model. These data suggest that statin treatment may be acceptable to protect myocardium in normocholesterolemic patients in acute coronary syndrome.