The aim of this study was to investigate the protective effects of notoginsenoside R1 ( R1) in the rat model ofmyocardial ischemia reperfusion injury and the possible mechanisms. Myocardial ischemia/reperfusion injury (MIRI) was induced by ischemia for 30 min and reperfusion for 60 min. Fifty male SD rats (250-300 g), were randomly divided into 5 groups: sham, model, R1 (20 mg/kg, 40 mg/kg, 60 mg/kg). The activities of serum lactate dehydrogenase (LDH), creatine kinase (CK), myeloperoxidase (MPO), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined after 60 min of reperfusion. Interleukin1 beta (IL-1 beta), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were evaluated by enzyme-linked immunosorbent assay (ELISA), VitaminD3 Upregulated Protein 1 (VDUP1), I kappa B alpha, P-I kappa B alpha, NF-kappa BP65, pNF-kappa BP65 were measured by western blotting. Our study demonstrated that R1 can ameliorate the impaired mitochondrial morphology and oxidation system; IL-1 alpha, IL-8 and TNF-alpha were recovered. Western blotting studies demonstrated that R1 substantially inhibited p-I kappa B alpha, NF-kappa BP65, p-NF-kappa BP65 protein levels and increased VDUP1 protein level. These findings suggest that R1 may effectively ameliorate the progression of 1/R injury and could be used as a therapy for patients with myocardial ischemia/reperfusion injury.