The Xuefuzhuyu capsule (XFZY) is widely used for the treatment of ischemic heart disease (IHD) in China. We previously demonstrated that XFZY could reduce apoptosis in Sprague-Dawley rat cardiomyocytes with the similar effect of resveratrol (Res) Hori et al. (2013), although its molecular mechanism underlying this protective effect is still unclear. Silent information regulator of transcription 1 (SIRT1) had been demonstrated to be responsible for cardioprotection against ischemia-reperfusion injury via long-term transcriptionally regulatory mechanism Braunersreuther and Jaquet (2012). Therefore, in the present study, we aimed to test if XFZY might contribute to the protection of ischemic myocardial cells induced by ischemia through SIRT1-mediated signal transduction pathway by using electron micrograph, RT-PCR assay, and western-blot test. All the result showed that the target genes of SIRT1 pathway including P53, NF-kB, FOXO1, FOXO3, and FOXO4 were significantly downregulated to SIRT1, suggesting that apoptosis pathway might transcriptionally be regulated to SIRT1. In addition, the expression level of SIRT1 was significantly increased by XFZ, it might prove that SIRT1 is the target of XFZY working on ischemia heart disease. Our findings supported that XFZY might function to protect myocardial cells and reduce myocardial injury though SIRT1 signaling pathway and has the same pharmacological effect with Res.