Abstract: Objective To study the effect of Wenyang Tongmai Fang(WTF) (Warming Yang and Invigorating Pulse-beat Prescription) on myocardial ischemia/ reperfusion (I/R) injury and its mechanism. Methods Thirty- six male SD rats were randomly divided into myocardial I/R injury group(IR group), WTF group, and WTF + blocking agent (BA) group. Their myocardial infarction size was measured with nitroblue tetrazolium staining (NBT). Apoptosis index (AI) was assayed by TUNEL, and expression of Akt and P-Akt was detected by Western blot. Results The myocardial infarction size was significantly smaller, the AI was significantly lower, and the expression level of P-Akt was significantly higher in WTF group than in IR group and WTF + BA group. Conclusion WTF Warming Yang and Invigorating Pulse-beat Prescription can protect myocardium against I/R injury and reduce myocardial apoptosis by activating the PI3K-Akt signal transduction pathway.