It has been reported that Qiliqiangxin (QL), a traditional Chinese medicine compound, could inhibit cardiac hypertrophy and remodeling, and improve cardiac function. However, whether and how it reverses cardiac remodeling in rats post myocardial infarction (MI) remains unknown. This study aims to explore related mechanisms linked with cardiac function improvement and attenuation of cardiac remodeling by QL in rats with experimental MI. MI was induced by ligation of left anterior descending coronary artery (LAD) in male Sprague-Dawley rats. Rats with LVEF < 50% at four weeks after procedure were treated for another 6 weeks with placebo, QL and captopril. Echocardiography and plasma NT-proBNP were measured at the end of study, and histological studies were performed. Protein expressions of Neuregulin-1 (NRG-1), total-Akt, phospho-Akt (Ser473), hydroxy-HIF-1α (Pro564), VEGF, Bax, Bcl-2 and Caspase 3 were examined by Western blot. mRNA expression of NRG-1 and p53 was detected by real-time PCR. Compared with the placebo group, QL improved cardiac function, reduced left ventricular dimension, inhibited interstitial inflammation and fibrosis, increased neovascularization, and attenuated cardiomyocyte apoptosis. Meanwhile QL significantly upregulated the expression of HIF-1α, VEGF, enhanced phosphorylation of Akt, decreased the ratio of Bax/Bcl-2 and Caspase 3 expression. Furthermore, we observed upregulation of NRG-1 and downregulation of p53 after QL treatment. Our data suggest that the beneficial effects of QL on improving cardiac function and attenuating cardiac remodeling post MI are associated with angiogenesis enhancement and apoptosis inhibition, which may be mediated via activation of NRG-1/Akt signaling and suppression of p53 pathway.