Objective:To investigate the beneficial effects and the potential molecular mechanisms of Berberine on cardiac hypertrophy induced by pressure overload in rats. Methods: Transverse aortic constriction (TAC) surgery was conducted to set cardiac hypertrophy model in rats. There were three groups: the sham group (n=8), the TAC group (n=8),and the TAC + Berberine group (n=8). Echocardiography was performed to evaluate the cardiac function 4 weeks after the TAC surgery. Histopathology staining, Masson trichrome staining, TUNEL staining, and other molecular biology methods were performed to measure myocardial cell size, cardiac fibrosis, myocardium cell apoptosis, and other indexes. The mRNA expression of atrial natriuretic factor (ANP) was detected by RT-qPCR. To evaluate endoplasmic reticulum (ER) stress level, Western blotting was carried out to test the expression of ER stress associated proteins Bip/GRP78 and CHOP. Results: Compared with the TAC group, Berberine significantly improved cardiac hypertrophy situation (P < 0.05), reduced myocardial interstitial fibrosis and cardiac apoptosis (P < 0.05). Western blotting showed that Berberine administration remarkably decreased the expression of Bip/GRP78 and CHOP induced by TAC surgry (P < 0.05). Conclusion: Berberine could protect hypertrophic myocardium by attenuating TAC-induced cardiac hypertrophy and dysfunction and inhibiting myocardial cell apoptosis, and that cardioprotective effect of Berberine is, at least in part, associated with reducing endoplasmic reticulum stress-meditated apoptosis.