Puerarin is an active ingredient of pueraria, which has been developed for puerarin injections, used in the treatment of cardiovascular diseases including arrhythmia, myocardial ischemia and hypertension. However, the molecular mechanisms of puerarin on ischemia/reperfusion (I/R)‑induced myocardial apoptosis in diabetic rats are not fully understood. The present study aimed to investigate whether puerarin can attenuate I/R‑induced myocardial apoptosis in diabetic rats, and to investigate the underlying mechanism. A hemodynamic analyzing system was employed to analyze the left ventricular developed pressure (LVDP), the left ventricular end‑systolic interior dimension (LVIDs) and the left ventricular end diastolic interior dimension (LVIDd). ELISA kits were used to analyze malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑6 levels, NO production and caspase‑3 activity. Nuclear factor (NF)‑κB, ascular endothelial growth factor A (VEGFA), angiotensin (Ang)‑I, phosphorylated (p)‑endothelial nitric oxide synthase protein expression was analyzed using western blot analysis. Puerarin significantly reduced the myocardial infarct area, and increased left ventricular developed pressure in diabetic rats with myocardial I/R. Oxidative stress, inflammation and nuclear factor‑κB protein expression were significantly reduced by puerarin. Furthermore, puerarin activated the protein expression levels of VEGFA and Ang‑I, and increased nitric oxide production, phosphorylated‑endothelial nitric oxide synthase protein expression and caspase‑3 activity. These results demonstrated that the myocardial protective effect of puerarin serves to reduce myocardial I/R injury, via upregulation of VEGFA/Ang‑1 and suppression of apoptosis, in diabetic rats with myocardial I/R.