Objective To evaluate the effect of different levels of doxorubicin-induced cardiotoxicity in mice by examining pathological changes. Methods In total, 36 male C57BL/ 6J mice (8 weeks old, SPF grade) were randomly assigned to the normal saline group ( NS group), 3 mg / kg doxorubicin group, 4 mg / kg doxorubicin group, 5 mg / kg doxorubicin group, 6 mg / kg doxorubicin group and 7 mg / kg doxorubicin group ( 6 mice in each group). Mice received intraperitoneal injection of saline or different concentrations of doxorubicin, 3 days/ times, 10 times in total. We monitored heart weight, body weight, ratio of body weight with heart weight, tibia to heart weight ratio, survival rate and evaluated cardiomyocyte apoptosis and cardiac fibrosis, simultaneously measured the cross-sectional area of heart and single myocyte cross-sectional area size. Results All six mice in each of the 3~ 5 mg / kg groups survived, with a survival rate of 100%. Five mice in the 6 mg / kg group survived, the survival rate was approximately 83. 3%. One mouse in the 7 mg / kg group survived, the survival rate was approximately 16. 7%. The survival rate of mice in the treatment groups decreased and was negatively correlated with doxorubicin concentration. The heart weight, body weight and heart to tibia ratio of mice in the treatment groups decreased in a dose-dependent manner. When the concentration of doxorubicin reached 4 mg / kg, the proportion of cardiomyocyte apoptosis increased, the area of myocardial fibrosis increased, and the cross-sectional area of the whole heart and cardiomyocyte decreased in the model groups compared with the NS group, and these differences were statistically significant (P<0. 05). Conclusions The indexes of cardiac fibrosis, cardiomyocyte apoptosis, atrophy and survival rate of mice worsen with the increase of doxorubicin accumulation in vivo. A concentration of 4 ~ 6 mg / kg doxorubicin is appropriate to build the model of chronic cardiotoxicity in mice, if doxorubicin exceeds this dose, the death rate of mice will be high, which is not conducive to the later experiment.