OBJECTIVE: To study the effects of simvastatin on oxidative stress and cell apoptosis in aged mice with myocardial ischemia-reperfusion (IR). METHODS: Aged mice were randomly divided into sham operation group (phosphate buffer solution), model group (phosphate buffer solution) and simvastatin low-dose, medium-dose and high-dose groups (2.5, 5 and 20 mg/kg) with 14 mice in each group. Those groups were given relevant medicine intraperitoneally before modeling for 7 d, once a day. IR model was induced in those groups except for sham operation group. The area ratio of myocardial infarction, myocardial cell apoptosis rate, activity of myocardial tissue apoptosis gene Caspase-3, the protein expression of Bax and Bcl-2, Akt phosphorylation, serum concent of MDA and activity of SOD were all detected. RESULTS: Compared with sham operation group, the area ratio of myocardial infarction, myocardial cell apoptosis rate, Caspase-3 activity, the protein expression of Bax and MDA content were all increased in model group, while the protein expression of Bcl-2, Akt phosphorylation and SOD activity were decreased (P<0.01). Compared with model group, the area ratio of myocardial infarction, myocardial apoptosis rate, Caspase-3 activity, the protein expression of Bax and MDA content were all decreased in simvastatin high-dose group, while the protein expression of Bcl-2, Akt phosphorylation and SOD activity were increased (P<0.01). There was no statistical significance in above indexes in simvastatin low-dose and medium-dose groups (P>0.05). CONCLUSIONS: Simvastatin can relieve myocardial IR injury in aged mice, and the mechanism of which may be associated with inhibiting myocardial cell apoptosis and the generation of oxidative stress.