Abstract Objective: To compare the effectiveness of applying different kinds of statins in treating ischemia-reperfusion injury on myocardium in rabbits. And then the related mechanisms in the diversity of protective effects were explored. Methods: Pravastatin, atorvastatin and fluvastatin were fed by nasogastric tube 2h before the ischemia-reperfusion injury respectively. 2h after injury, the area of myocardial infarction and the activity of the endothelial nitric oxide synthase (eNOS) in ischemia-reperfusion injured myocardial tissues were measured. In vitro, the human umbilical vein endothelial cells (HUVECs) were treated with the three kinds of statins, and then the expression of eNOS and the related signal molecule p-Akt were measured in statins-treated HUBECs respectively. Results: In vivo, the atorvastatin-treated group had significantly fewer size of infracted myocardium and higher level of eNOS than the other two statins-treated groups at the same dose of 50mg/kg (P<0.01). In vitro, atorvastatin-treated HUVECs had higher amounts of active eNOS (P<0.05) than the other two statins-treated HUVECs and expressed much more p-Akt. Conclusion: Atorvastatin attenuated ischemia-reperfusion injury more effectively than pravastatin and fluvastatin. And the stronger ability in activating p-Akt signal passage as well as the increased pruduction of eNOS in endothelial cells induced by atorvastatin were suggested to be one of the mechanisms in the protective effects.