Recently, various clinical studies have indicated that lipophilic beta-blockers reduce the coronary mortality in diabetic patients; however, systematic studies have not been reported. The objective of the present investigation was to compare the effects of chronic treatment with metoprolol and atenolol on cardiovascular complications in streptozotocin (STZ)-induced diabetic rats. Injection of STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, cardiac hypertrophy, reduction in heart rate, and structural alterations in cardiac tissues. Metoprolol and atenolol effectively prevented the development of hypertension in diabetic rats. Metoprolol treatment produced a slight but significant reduction in serum glucose levels with elevation in serum insulin levels, while atenolol produced a slight increase in glucose levels but no effect on insulin levels. Moreover, neither metoprolol nor atenolol treatment reduced the elevated cholesterol levels in diabetic rats. Metoprolol treatment significantly prevented STZ-induced increase in triglyceride levels, but atenolol failed to produce this effect. Metoprolol exhibited a minimal improvement in STZ-induced bradycardia, whereas atenolol produced a further reduction in heart rate. Histological examination showed metoprolol treatment also prevented STZ-induced hypertrophy and some of the alterations in cardiomyocytes. In conclusion, our data suggest that metoprolol has some beneficial effects over atenolol with respect to cardiovascular complications associated with diabetes mellitus.