Objective To observe and compare the effects of gender and injection doses on isoproterenol ( ISO) induced cardiac hypertrophy model in rats. Methods Male and female SD rats were randomly divided into three groups as follows: normal control group, low dose of group (1. 25 mg / kg) and high dose of group (5 mg / kg). Ten days after the subcutaneous injection of ISO, the differences in the parameters from echocardiography, hemodynamics, histopathology and Real-time PCR were compared. Results (1) After treatment with two doses of ISO, various parameters of heart weight, interventricular septum thickness, myocardial cell area, myocardial fibrosis and mRNA expression levels of ANP and BNP were significantly increased (P< 0. 01), while left ventricular function was significantly reduced in rats (P< 0. 01). (2) The changes of left ventricular weight / body weight, interventricular septum thickness, left ventricular end-systolicpressure (LVESP), left ventricular pressure maximal rate of fall (-dp / dtmax ) and ANP mRNA expression were significantly increased or decreased in a dose-dependent manner in male rats ( P < 0. 01). However, only the left ventricular end- diastolicpressure(LVEDP),left ventricular pressure maximal rate of fall( dp / dtmax) was decreased in a dose-dependent manner in female rats. (3) Female rats exhibit a severe reduction in cardiac function than male rats when injected with low- dose of ISO (P< 0. 01). In contrast, male rats exhibited a significant increase in left ventricular weight / body weight and ANP mRNA expression than female rats when injected with high-dose of ISO (P< 0. 01). (4) In male rats, the survival rate of low- and high- dose of groups of ISO were 63. 6% and 81. 8%, respectively. The survival rate of low- and high- dose of groups in female rats were 63. 6% and 55. 0%, respectively. Moreover, no rats died in the normal group. Conclusions The dose of injection has a greater effect on the degree of cardiac hypertrophy in male rats induced by ISO. It is best to choose a dose of 5 mg / kg for male rats and 1. 25 mg / kg for female rats to establish an ISO-induced cardiac hypertrophy model.