Objective To explore the long-term effects of uncoupling protein 1 (Ucp1) knockout on isoproterenol- induced myocardial remodeling in rats. Methods To establish the myocardial remodeling models, saline or isoproterenol was administered intraperitoneally at 30 mg / kg once per day for 3 consecutive days in wild-type (WT) and Ucp1 knockout (Ucp1^{- / -}) rats at 2 months of age. The phenotype analysis of the WT and Ucp1^{- / -}rats was analyzed using M-mode echocardiography, the serum markers of myocardial injury lactate dehydrogenase (LDH) and creatine kinase isoenzyme MB (CK-MB), and histopathological examination at 1 month after the saline or isoproterenol administration. Results In the saline group, the echocardiographic parameters, serum marker of myocardial injury CK-MB, and fibrosis were comparable between the WT and Ucp1^{- / -}rats. In the model group, Ucp1^{- / -}rats had thin-walled ventricles and decreased cardiac function, and had higher serum LDH and CK-MB levels and more serious myocardial disarray and fibrosis in the heart tissue compared with WT rats. Conclusions Ucp1 knockout aggravates isoproterenol-induced myocardial remodeling in rats. Ucp1 may be an important modifier gene of myocardial remodeling.