Objective <p>To study the potential cardioprotective role of dapagliflozin in comparison to metformin in experimentally- induced myocardial infarction in rats with type 2 diabetes mellitus (T2DM).</p> Materials and Methods <p>This study was comparative study, which was housed at the animal house, Mansoura Experimental Research Center (MERC). Fifty adult male albino rats were included in this study and there were further randomly divided into Group-I: (Normal), Group –II: rats received Streptozotocin (STZ) for induction of type 2 DM. This group was subdivided into (4) equal subgroups as the following: Group –IIa: (DM), Group-IIb: (DM+ISO), Group–IIc: (DM+ISO+Metformin), Group-IId: (DM+ISO+DAPA). The outcomes of the study were measured by ECG recording, serological study which included Interleukin (IL)-10, IL6, and tumor necrosis factor (TNF)-α, troponin, lipid profile and blood glucose and histopathological examination of isolated hearts.</p> Results <p>Dapagliflozin show better cardioprotective effect than Metformin with lower IL-10, IL-6, TNF, CTNI and Troponin C levels than Metformin with statistically significant difference (<i>p</i> &lt; 0.001*). The percentage of area of edema and degeneration is the lowest in controls followed by DM+ISO+DAPA group then DM+ISO+Metformin group when compared with DM and DM+ISO groups which revealed the cardio protective effect of DAPA and Metformin with inter-groups statistically significant difference (<i>p</i> &lt; 0.001*)</p> Conclusion <p>Dapagliflozin has cardioprotective effects against myocardial infarction in type 2 diabetic rats. This effect might be due to its antifibrotic and antiarrhythmic effects. However, Metformin did not show any antifibrotic or anti-arrhythmic effects.</p>