Context: Ginsenoside Rg1 (Rg1), as the active ingredient of Panax notoginseng, has protective effect on the cardiovascular system. While, the efficiency of Rg1 against acute myocardial infarction (MI) is not fully elucidated. The aim of this study was to investigate the cardio-protection and the underlying mechanism for Rg1. Objective: Myocardial infarction was induced by ligation of the left anterior descending coronary artery of wistar rats. 2,3,5-triphenyltetrazolium chloride (TTC) stain assay was used to detect infarct size; hematoxylin and eosin (HE) and phosphotungstic acid-hematoxilin (PTAH) stain assay were used to evaluate the cardiac structure; terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to detect apoptosis; immunohistochemical stain was used to evaluate neutrophils and macrophages infiltration. Key Findings: Firstly, Extract Rg1 (P < 0.01) and Ferment Rg1 (P < 0.01) down-regulated myocardial infarct size and up-regulated superoxide dismutase (SOD) activity significantly. Then, HE and PTAH stain indicated the protection of Extract Rg1 and Ferment Rg1 on heart structure, especially on the integrity of sarcomere. Finally, both Extract Rg1 (P < 0.001) and Ferment Rg1 (P < 0.001) reduced the number of apoptosis cells, and further inhibited the infiltration of neutrophils into the infarct site of heart. Summary: For the first time, our present study verified the efficiency of Rg1 against acute MI, and provided experimental evidence that Ferment Rg1 holds similar cardio-protection with Extract Rg1. Rg1 holds potential therapeutic value for further drug development on heart disease.