To determine whether albuminuria is associated with insulin resistance in patients with type II (non-insulin-dependent) diabetes mellitus, we performed hyperinsulinemic (40 mU/m2/min) euglycemic clamp studies in patients with a urinary albumin excretion (UAE) rate greater than 30 mg/24 h and in patients with a UAE less than 30 mg/24 h. The UAE-positive group (n = 22) did not differ significantly from the UAE-negative group (n = 18) with respect to age, sex, treatment of diabetes, body mass index, fasting or postload blood glucose or plasma insulin levels, blood pressure, or known duration of diabetes. The mean glucose disposal rate (GDR) was significantly lower in the UAE-positive group than in the UAE-negative group (3.44 +/- 0.29 v 4.75 +/- 0.52 mg/kg/min, P < .05). When patients with hypertension were excluded, GDR was still markedly lower in the UAE-positive group than in the UAE-negative group (3.89 +/- 0.54 v 6.68 +/- 0.71 mg/kg/min, P = .01). The difference between groups persisted even after adjustment for body mass index, sex, and hypertension (ANCOVA; P < .05). These results indicate that the presence of microalbuminuria is associated with impaired insulin action in patients with type II diabetes mellitus.