【Abstract】 Objective To investigate the alteration and the role of dynamin-related protein 1 (Drpl) in cardiac remodeling after myocardial infarction (MI). Methods The mouse model of MI was successfully established by the ligation of the left main descending coronary artery. Ultrasound echocardiography was to evaluate cardiac function and then the hearts were removed and stained with Masson to measure the myocardial fibrosis area. qRT-PCR and western blotting were used to detect the mRNA and protein expression of Drpl, respectively. In vitro, mouse cardiac myocytes (MCMs) were incubated in hypoxic environment (1 % O2， 5% CO2 , 94% N2 ; 8h). The alterations of Drpl were detected by fluorescent staining. The intracellular reactive oxygen species (ROS) level was tested by DHE staining and the contents of superoxide were measured by chemiluminescence. The apoptosis of cardiomyocytes were measured by Caspase-3 and TUNEL staining. Results MI obviously increased the expression of Drpl in mRNA (PV0. 01) and protein level (PV 0. 01). In contrast, the left ventricular fractional shortening ( LVFS) ( P<0.05 ) , left ventricular ejection fraction (LVEF) (P<0.05) and the fibrosis area were preserved by the inhibition of Drpl (Mdivi-1, the inhibitor of Drpl) (P<0. 05). The expression of Drpl was significantly elevated in cells treated with hypoxic. The elevated generation of ROS (P<0.01) , augmented production of Caspase-3 (PV0. 01) and increased apoptotic ratio of myocardial cells (P<0.01) were partly attenuated by the suppression of Drpl. Conclusion The inhibition of Drpl protected against adverse remodeling after MI in mouse through inhibiting oxidative stress and cell apoptosis.