Objective To analyze the dose dependent cardiotoxicity of cyclophosphamide and thus establish the mouse models for understanding the underlying mechanisms . Methods Thirty mice ( 7 -8 weeks old) were randomly divided into 6 groups:control of one course group ,control of two courses group , one course of low dose ( 50 mg/kg) group ,two courses of low dose group ,one course of high dose ( 100 mg/kg) group ,two courses of high dose group . The changes of cardiac function and morphology were analyzed at indicated times by ultrasound and histology respectively . Results Compared with the control groups , injection of low dose cyclophosphamide either with one course or two courses ,and injection of high dose with only one course had no in statically significant changes in hair color ,physical activity ,body weight and cardiac function( P > 0 .05) . Treatment of two courses with high dose resulted in significant decrease of physical activity and body weight ( P < 0 .05 ) . Meanwhile ,cardiac systolic function was significantly decreased( P <0 .05) . Histology study revealed robust cardiac hypertrophy and fibrosis . Conclusions Two courses of intraperitoneal injection of cyclophosphamide at high dose result in obvious cardiotoxicity , especially systolic dysfunction .Intraperitoneal injection of two courses of cyclophosphamide serves as a good strategy to induce cardiotoxicity in mice ,which could be applied for future mechanism study .