Cardiomyopathy specifically affects the structure and function of the heart muscle. It is the leading cause of death. Our aim was to elucidate role and therapeutic mechanisms of empagliﬂozin on cardiac dysfunction induced experimentally in non-diabetic rats by three different models for 13 weeks. 64 male Albino rats were divided in 8 groups (n=8). 1A received 1ml saline daily by oral gavage for 8 weeks. 2A, 3A were subjected to High Salt and Fat diet for 8,7 weeks respectively, 4A were injected with Doxorubicin intraperitoneally at weekly doses of 5 mg/kg for 5 weeks then treated with Empagliflozin daily from 8th week at a dose of (10 mg/kg) daily by oral gavage for 5 weeks in groups 1B, 2B, 3B, 4B. Body weight (BW), Systolic blood pressure (SBP), Electrocardiograph (ECG), Echocardiography were recorded at the start, 8th week and at the end of the experiment. At the end of the study, Heart /Body weight (HW/BW) ratio was measured, blood samples for estimation of serum glucose, cholesterol, triglycerides and (BNP) levels, while heart homogenate for (TNFα) and (MDA) estimation. Empagliflozin lowered BW (except increased in DOX), blood pressure, HW/BW ratio in all groups. Improved ECG ischemic changes (HFD), QT prolongation in (DOX), Systolic and diastolic function in ECHO. Biochemically, glucose, cholesterol and triglycerides levels were decreased in (HFD) in addition to reduced serum BNP, TNF and MDA of heart homogenate in all groups. Empagliflozin had a cardio protective that may be related to its anti-inflammatory, antioxidant effect.