The objective of this study is to demonstrate the cardioprotective effects of Salvia Miltiorrhiza Radix (SMR) on the pressure overload (PO)-induced heart failure (HF) by transverse aortic constriction (TAC) in C57BL/6 mice through possible antioxidant effects. Methods: The mortality, body and heart weights, antioxidant defense system of the heart and histopathology of heart were analyzed. The obtained results were compared with resveratrol, in which potent cardioprotective effects on TAC mice model were already proved at a dose level of 10 mg/kg by antioxidant effects, as reference in this experiment. Results: Significant increases of mortalities, heart weights, and hypertrophic, lytic and focal fibrotic histological changes in the left ventricles were found with defects of heart antioxidant defense systemsthe increases of heart cortex MDA contents, decreases of GSH contents, SOD and CAT activities in TAC control mice as compared with sham vehicle control mice, respectively. However, these HF signs induced by TAC surgery through PO and destroys heart antioxidant defense systems were significantly and dose-dependently inhibited by 14 days continuous oral treatment of SMR 500, 250 and 125 mg/kg, similar to those of resveratrol 10 mg/kg in SMR 125 mg/kg. Conclusions: The results obtained in this study propose that oral administration of SMR potently alleviates PO-induced HF by TAC, through augmentation of heart antioxidant defense system.