Background and objective: Recent clinical trials have shown that metformin improves clinical cardiovascular outcome in type-2 diabetic patients independently of its insulin-sensitizing effect. This study was sought to evaluate the potential cardioprotective effects of metformin on isoproterenol-induced cardiac stress in diabetic and non-diabetic rats. Materials and Methods: Diabetes was induced by using streptozocin (60 mg/kg, i.p.) while non-diabetic rats received saline. Rats in both experimental groups were then randomized to receive different doses of metformin (75, 150, 300 mg/kg i.p.) for 6 weeks. Cardiac stress was induced by isoproterenol (150 mg/kg i.p.) for two successive days. Specific biomarkers of tissue injury, namely brain natriuretic peptide (BNP), cardiac troponin-T (cTn-T), matrix metalloproteinase (MMP), tissue necrotic factor-α (TNF), were assessed. Data were analysed using one-way ANOVA followed by Newman Keuls post hoc test Results: The results showed that metformin significantly limited isoproterenol-induced myocardial injury in both diabetic and non-diabetic rats. Metformin significantly decreased the elevated serum levels of brain natriuretic peptide (BNP), matrix metalloproteinase (MMP), cardiac troponin t (cTn-T) which was induced by isoproterenol. It also limited expression of tissue necrotic factor-α (TNF-α) following the cardiac injury in diabetic and non-diabetic rats.