Decreased serum dehydroepiandrosterone (DHEA) concentrations may be associated with an increased risk of cardiovascular disease (CVD) in men. We evaluated relationships between serum DHEA sulfate (DHEA-S) concentration and carotid atherosclerosis, as well as major cardiovascular risk factors, in men with type 2 diabetes. Serum DHEA-S concentrations were measured in 206 consecutive men with type 2 diabetes. Relationships were analyzed between serum DHEA-S concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score (PS), as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations. Negative correlations were found between DHEA-S concentration and IMT (r = -0.298, P < 0.0001) and between DHEA-S concentration and PS (r = -0.308, P < 0.0001). IMT and PS were significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/ml) than in patients with higher concentrations of DHEA-S (1.07+/-0.30 mm versus 0.91+/-0.19 mm, P < 0.0001, and 5.5+/-4.2 versus 3.1+/-3.4, P < 0.0001, respectively). A negative correlation was found between serum DHEA-S concentration and age (r = -0.488, P < 0.0001). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of IMT (beta = -0.289, P < 0.0001) and of PS (beta = -0.301, P < 0.0001). In conclusion, serum DHEA-S concentration is negatively associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.