To evaluate the relationship of plasma endothelin-1 (ET-1) levels, a marker of endothelial dysfunction, and urinary albumin excretion in patients with type 2 diabetes mellitus (DM). Cross-sectional study was conducted in 279 patients (132 males, mean age: 58.7+/-11.0 years, mean DM duration: 11.3+/-8.1 years). Urinary albumin excretion, ET-1, and insulin were measured. Insulin sensitivity was estimated by homeostasis model assessment (HOMA-ir) index. ET-1 was associated with urinary albumin excretion after controlling for age, gender, body mass index, blood pressure, HbA1c test, and total cholesterol (R=0.436; adjusted R(2)=0.190, P<0.01). Furthermore, there was a progressive increase in plasma ET-1 levels from patients with normoalbuminuria (n=187, 0.92+/-0.50pg/ml), microalbuminuria (n=68, 1.13+/-0.52pg/ml) to macroalbuminuria (n=24, 1.93+/-1.10pg/ml, P<0.01). There is an independent association of plasma ET-1 levels with urinary albumin excretion. In addition, plasma ET-1 levels started to increase in the normal values of urinary albumin excretion suggesting that in patients with type 2 DM endothelial dysfunction is already present, in urinary albumin excretion values considered normal.