Background: Diabetes Mellitus is the most common endocrine disorder. It is a pathological state leads to long term complications causing damage of different tissue and organs as heart and blood vessels. Hypertension is one of the leading causes of mortality and morbidity. Melatonin has extraordinary antioxidant potential and reduce the level of free radical burden on the level of both oxygen and nitrogen species. Objective: Evaluation of melatonin on hypertension and diabetes induced experimentally in adult male albino rats. Materials and Methods: Seventy adult male albino rats of local strain were divided into equal seven groups as follow: Group I: served as control group received normal saline, Group II: diabetic group, Group III: hypertensive group, Group IV: Diabetic-hypertensive group, Group V: diabetic-melatonin-treated group, Group VI: Hypertensive-melatonin-treated group and Group VII: Diabetic-hypertensive-melatonin-treated group. At the end of experimental period, blood samples were obtained for detwrmination of glycated hemoglobin, plasma glucose, serum lipid profile (total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG)), serum insulin, serum urea and serum creatinine levels. Measurments of blood pressure were performed for the hypertensive rats. Also, cardiac muscles samples were obtained for histopathology study. Results: STZ led to significant increase in blood glucose, glycated hemoglobin, cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant decrease in serum insulin level.Cadmium led to significant increase in total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in blood pressure. Melatonin treatment led to significant decrease of blood glucose, glycated hemoglobin, total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in serum insulin level associated with significant decrease blood pressure. Conclusion: Melatonin has a protective effect against cardiac muscle abnormalities in diabetic, diabetic-hypertensive and hypertensive rats due to its antioxidant properties.