In this study, we investigated whether lentivirus-mediated gene transduction improves the cardiac function in rats with myocardial infarction and the mechanisms involved.Briefly, lentivirus carrying human neuregulin-1 (hNRG-1) gene was injected into infarcted myocardium of rats. Four weeks later, lentivirus-mediated gene transduction promoted hNRG-1 gene and protein expression. Overexpression of hNRG-1 increased the number of microvessels in the ischemic myocardium and decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-stained positive cells. Furthermore, qRT-PCR assay showed that hNRG-1 was capable of increasing the expression of bcl-2 and VEGF-A while decreasing the expression of bax. Western blot analysis suggested that overexpression of hNRG-1 activated the PI3K/Akt pathway and increased the phosphorylation of Akt and eNOS.These findings suggest that NRG-1 gene transduction can improve cardiac function by promoting angiogenesis and preventing apoptosis.