Tanshinone IIA (Tan IIA), a derivative of phenanthrenequinone isolated from Salvia miltiorrhiza, has been widely used for treating cardiovascular diseases in China. In the present study, we assessed the effect of Tan IIA on cardiac function, vascular endothelial growth factor (VEGF) expression and angiogenesis on models of myocardial infarction (MI) in rats. The results demonstrated that TanIIA elicited a significantly cardioprotective effect by improving heart function, reducing infarct size, and increasing survival rate in MI rat. Our results offer, for the first time, further insight into Tan IIA promoting angiogenesis and up-regulating VEGF expression in MI rats due to the enhancement of hypoxia-inducible factor 1alpha mRNA expression, and provide a novel target for Tan IIA in the prevention and treatment of myocardial ischemia injury.