The level of sex hormone-binding globulin (SHBG) is associated with glucose metabolism in nondiabetic women and men, and the finding of low SHBG levels is suggested to be a predictor of the development of type 2 (noninsulin-dependent) diabetes mellitus. To further assess the relationship between SHBG levels and glucose metabolism, we measured serum concentrations of sex hormones and SHBG in 23 well characterized diabetic men, and studied the relationship between these variables and parameters of glucose and lipid metabolism. Insulin sensitivity was estimated using the hyperinsulinemic euglycemic glucose clamp technique. There was a strong positive correlation between the level of SHBG and the sensitivity to insulin in these individuals (r = 0.74; P < 0.001), which was independent of obesity and abdominal fat accumulation. Controlling for the effect of fasting C-peptide and insulin levels did not change the correlation coefficient significantly. SHBG levels did not correlate with levels of free testosterone (F-T), free estradiol (F-E2), or F-T/F-E2 ratio. F-E2 was positively correlated with levels of diastolic blood pressure and triglycerides (r = 0.44; P < 0.05 and r = 0.62; P < 0.001, respectively). These findings support earlier observations that associate insulin resistance with levels of SHBG, and for the first time demonstrate a direct correlation between sensitivity to insulin and SHBG levels in men with type 2 diabetes.