Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague-Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED (P < 0.01), QTc interval (P < 0.001), the ratio of karyolysis and karyorrhexis (P < 0.001) and infiltrative cell proliferation (P < 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group (P < 0.001). In the DOX+EMPA group, LVEDD (P < 0.05) and LVESD (P < 0.01) values, QTc interval (P < 0.001), karyolysis and karyorrhexis ratios (P < 0.001) and infiltrative cell proliferation were lower (P < 0.01); normal cell morphology and EF were higher compared to the DOX group (P < 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity.