【Abstract】Objective To investigate the effect and mechanism of ginsenoside Rb3 in the development of Doxorubicin (DOX)induced cardiotoxicity. Methods SD rats were randomly divided into control group, DOX (25 mg/kg) group, DOX+ ginsenoside Rb3 (20 mg/Kg) and DOX+GRb3+ Wortmanin (1mg/Kg/d). The model of myocardial toxicity was established by intraperitoneal injection of DOX 6 times in 14 days. The protective effect of ginsenoside Rb3 on cardiotoxicity induced by DOX was observed. Myocardial pathological changes were observed by H&E staining in rats. The levels of myocardial injury markers, inflammatory factors, oxidative stress were detected by ELISA kit. The protein expression levels of pPI3K, PI3K, pAKT and AKT were detected by Western Blotting. Results DOXinduced cardiotoxicity resulted in increased myocardial damage and increased inflammation and oxidative stress. The GRb3 could improve the heart damage caused by DOX, mainly in the significant reduction of collagen accumulation and the decrease of myocardial injury marker levels. Simultaneous treatment with ginsenoside Rb3 significantly inhibited DOXinduced myocardial inflammation and oxidative stress. In the mechanism study, we found that ginsenoside Rb3 could activate PI3K/AKT signaling pathway in DOXinduced cardiotoxicity injury, and PI3K/AKT inhibitor Wortmanin could reverse the protective effect of ginsenoside Rb3 on myocardium. Conclusion Ginsenoside Rb3 can improve DOXinduced cardiotoxicity by activating the PI3K/AKT pathway.