Background: Myocardial ischemia is one of the most serious complication that results from metabolic syndrome (MetS). MetS is usually treated by polytherapy to decrease the risk of comorbidities. Dipeptidyl peptidase -4 (DPP-4) inhibitors are commonly used to control hyperglycemia and insulin resistance associated with MetS. Objective: The aim of the present study was to demonstrate the effect of linagliptin (DPP-4 inhibitor) on some ECG and biochemical parameters of myocardial infarction (acute myocardial ischemia) induced by isoprenaline in rats with metabolic syndrome. Methodology: 32 male albino rats of local strain were divided into four groups, Group I (8rats): Control normal group, rats were allowed to feed normal rat chow diet and water ad libitum. Group II (8 rats): Metabolic non ischemic group, animals of this group were allowed to feed high fat diet (HFD) with sucrose in drinking water for twelve weeks. Group IIIa (8 rats): Metabolic ischemic non treated group; rats of this group were allowed to feed HFD with sucrose in drinking water for twelve weeks followed by injection of isoprenaline (85/ kg / day) S.C for two consecutive days at the last two days of study period. Group IIIb (8 rats): Metabolic ischemic group treated orally with linagliptin 0.45mg/kg once daily for 4 weeks before injection of isoprenaline. Results: Linagliptin produced a significant reduction in heart rate and S-T segment as compared to metabolic ischemic group. In addition, it produced a significant reduction in creatine kinase myocardial band (CKMB), malondialdehyde (MDA), tumor necrosis factor α (TNFα) and significant increase in catalase enzyme level as compared to ischemic non treated group. Conclusion: linagliptin is a promising drug for decreasing the incidence of myocardial infarction which may complicate MetS.