Abstract: AIM:To compare two chronic heart failure (CHF) mouse models established, respectively, by aortic arch constriction or by isoprenaline hydrochloride (IPH). METHODS: Adult C57BL mice were randomly divided into four groups: natural control group (N), sham-operation group (A), IPH injection-induced model group ［15 mg/(kg·day), 11 days (B)］ and aortic arch constriction-induced model group (C). Heart weight to body weight ratio (HW/BW), left ventricular internal diameter at end-diastole (LVEDD), left ventricular internal diameter at end-systole (LVEDS), left ventricular ejection fraction (EF) and LV fractional shortening (FS) were measured after 8 weeks. The expression levels of ANP, BNP, and α-MHC in heart tissues and the size of cardiomyocytes were also observed. RESULTS: Both IPH injection and aortic arch constriction successfully established experimental models of CHF. Compared with those in the N group, LVEDS increased by 36.06%, EF and FS decreased by 24.88% and 29.22%, respectively (P<0.05), and cell numbers/1 mm2 increased by 24.80% (P<0.01) in group B. HW/BW significantly increased (P<0.01), LVEDD and LVEDS increased, respectively, by 27.42% and 54.81%, LVEF and FS decreased by 37.40% and 42.17%, respectively (P<0.01), and cell numbers/1 mm2 increased by 48.39% (P<0.01) in group C. HW/BW and cell numbers/1 mm2 in group C significantly increased compared with those in group B (all P<0.01). CONCLUSION: CHF mouse model induced by aortic arch constriction may well mimic the pressure overload-induced heart failure, and its pathophysiological development is similar to the pressure overload-induced heart failure. CHF mouse model induced by aortic arch constriction is an ideal model of CHF over IPH injection method.