Abstract: ob＜x＞jective To investigate the protective effect of genistein (Gen) on doxorubicin (Dox) induced cardiotoxicity and its possible mechanism. Methods Twenty-four SD rats were randomly divided into control group (Ctrl), genistein group (Gen), doxorubicin induced group (Dox) and genistein treated group (Dox + Gen). Except Ctrl group, the other groups were given corresponding drugs for 6 weeks. After the dosage computation in the rat heart heavy weight/body weight ratio and body length/tail length ratio, fasting blood detection of creatine kinase(CK), lactate dehydrogenase(LDH)content, HE staining was used to observe the morphological changes of myocardial tissue in rats, immunohistochemical technique in the detection of myocardial tissue of rats Caspase-3 ex＜x＞pression, superoxide anion fluorescent probe (Dihydroethidium, DHE) dyeing semi-quantitative method to detect fluorescent ex＜x＞pression of rat myocardial cell H9C2, the ex＜x＞pression of apoptotic protein Caspase-3 was detected by Western Blot. Results The ratio of heart weight/body weight and body length/tail length of rats in each group changed slightly, but the differences were not statistically significant (P> 0.05).Serum contents of CK and LDH in Dox group were significantly higher than those in Ctrl group (P< 0.01), the above indexes in Gen + Dox group were significantly lower than those in Dox group (P< 0.01).The myocardial tissue in the Dox group showed patchlike necrosis, increased myocardial fibers and obvious apoptosis of myocardial cells, while the myocardial cells in the Gen + Dox group were arranged neatly, with clear structure and few myocardial fibers.Compared with the Ctrl group, the fluorescence ex＜x＞pression of DHE and the ex＜x＞pression of Caspase-3 protein in Dox group were significantly up-regulated (P< 0.01), the fluorescence ex＜x＞pression was decreased after the addition of Gen, and the ex＜x＞pression level of Caspase-3 protein was significantly down-regulated (P< 0.01).Conclusion Gen may reduce the cardiotoxicity induced by doxorubicin by alleviating oxidative stress, down-regulating the ex＜x＞pression of Caspase-3 protein and thus play a protective role in the cardiotoxicity induced by doxorubicin.