The intrinsic capacity of the heart to regenerate and replace damaged myocardium by promoting cardiac stem cell differentiation is one of the key repair mechanisms following acute injury to heart. Mitochondrial dysfunction plays an important role in various heart disorders including myocardial infarction. Micro RNAs are implicated in pathogenesis of various cardiac diseases. Cardiac specific miR-499 was shown to regulate mitochondrial fission by inhibiting Drp-1 (Dynamin-related protein). We hypothesize that mitochondrial division inhibitor (Mdivi-1) ameliorates adverse post myocardial infarction remodeling by increasing the expression of miR-499 thereby promoting the ventricular cardiac stem cell differentiation . To verify this, we created myocardial infarction in wild type (C57BL6/J) animals and treated them with Mdivi-1(50mg/kg BW) for 4 weeks. Cardiac function was assessed by echocardiography and pressure volume loop. Individual micro RNA assay was performed to compare miR-499 expression among the groups. Endogenous cardiac stem cell expression was assessed by C-kit marker. Our results showed that Mdivi-1 promotes miR-499 expression and cardiac stem cell differentiation. Echo data revealed improved ejection fraction and left ventricular function. Based on these findings we conclude that Mdivi-1 ameliorates adverse post myocardial infarction remodeling by promoting miR-499 expression and cardiac stem cell differentiation.