Hsp90 is a molecular chaperone that contributes to the activation and stabilization of client proteins. In our previous studies, we found that an inhibition of Hsp90 reduced cardiac remodeling during the development of heart failure in rodents. Simvastatin, an antihyperlipidemic drug, was shown to inhibit Hsp90. However, it is still unclear whether simvastatin attenuates cardiac remodeling via inhibition of Hsp90. Therefore, we investigated effects of simvastatin on the development of heart failure following myocardial infarction in rat. The results showed that treatment of the animals with simvastatin attenuated the development of cardiac fibrosis. Furthermore, we found that simvastatin attenuated the interaction of Hsp90 with c-Raf and calcineurin and decreased their contents. These results suggest that Hsp90 inhibition by simvastatin treatment is, at least in part, responsible for the reduction in the development of myocardial remodeling following acute myocardial infarction.