Astragalus membranaceus extract (AME) is a widely used herbal product for the treatment of cardiovascular diseases in China. The present study aimed to evaluate the cardiac protective effects of AME, and to probe the underlying molecular mechanism related to angiogenesis. In this study, AME with 75 microg/mL significantly increased proliferation, migration and tube formation on human umbilical vein endothelial cells (HUVECs). Moreover, in vivo experiments on rats with ligation of left anterior descending artery were performed to study the cardiac protective and angiogenic effect of AME (50 and 100 mg/kg i.g. for 3, 7, 14 days). The results showed that AME inhibited cardiac fibrosis, reduced infarct size, and increased capillary and arteriole densities. Meanwhile, western blot was used to determine protein levels of VEGF, p-AKT, p-GSK3beta and p-mTOR. AME significantly elevated protein expression of VEGF and increased phosphorylation of AKT, GSK3beta and mTOR. In conclusion, AME exerted cardiac protective and angiogenic effects in the ischemic injured heart. The activation of AKT/GSK3beta and AKT/mTOR pathways and elevated expression of VEGF may contribute to the promoted neovascularisation by AME.