Objective To investigate whether there are gender differences in cardiac remodeling induced by chronic sympathetic activation. Methods Mice were randomly divided into four groups: male control, male isoprenaline (ISO), female control, and female ISO groups. A cardiac remodeling model was established by subcutaneous injection of ISO for 14 days. The ratio of heart weight to body weight (HW/ BW) and the ratio of heart weight to tibia length (HW/ TL) were used to assess cardiac remodeling; Cardiac function was assessed using echocardiography to determine diastolic left ventricular posterior wall thickness ( LVPW;d). Hematoxylin and eosin staining was used to determine myocyte cross- sectional area. Picric-sirius red staining was used to evaluate cardiac fibrosis. Results Compared with the control group, the HW/ BW and HW/ TL ratios were increased by 9. 1% (P<0. 05) and 42. 8% (P<0. 001), respectively, in the male ISO group and by 12. 9% and 9. 5% (all P<0. 05), respectively, in the female ISO group. The increase was significantly greater in the male ISO group (19. 8%, P< 0. 01) than in the female ISO group. Compared with the control group, the myocyte cross-sectional area in the male ISO group increased by 19. 1% (P<0. 0001), while that in the female ISO group increased by 6. 9% (P< 0. 05). The increase was significantly greater in the male ISO group ( P< 11. 6%) than in the female ISO group. There was no significant difference in cardiac function among groups. Compared with the control group, the cardiac fibrosis area of the male ISO group increased by 158% (P<0. 0001) and by 39. 7% (P<0. 05) in the female ISO group. Compared with the female ISO group, the fibrosis area of the male ISO group increased by 119% (P<0. 0001). Conclusions There are gender differences in cardiac remodeling induced by chronic sympathetic activation. Greater cardiac hypertrophy and cardiac fibrosis occur in male mice compared with female mice.