We investigated the effect of insulin on urinary excretion of phosphate in type II diabetes mellitus (DM) with respect to the absence or presence of renal insufficiency. A euglycemic-hyperinsulinemic clamp was performed in 37 type II DM patients. Subjects were divided into two groups: group A consisted of patients with serum creatinine levels less than 1.5 mg/dL (n = 22), and group B consisted of patients with serum creatinine levels of 1.5 mg/dL or greater (n = 15). Blood and urine samples were collected at the beginning and end of the clamp, and urinary excretion of phosphate was evaluated by calculating fractional excretion (FE-P). Tissue sensitivity to insulin in the whole body was expressed as the glucose infusion rate (M value) and that divided by steady-state plasma insulin levels (M/I ratio) during the last 30 minutes of the clamp. FE-P in group A patients significantly decreased during the clamp (from 9.46 +/- 0.67% before the clamp to 7.12 +/- 0.73% after the clamp, P < .004), whereas FE-P in group B patients did not change significantly during the clamp. The percent decrease of FE-P (decrease of FE-P during the clamp divided by FE-P before the clamp) in group A patients was significantly higher than in group B patients (22.5 +/- 7.0% and 2.5 +/- 5.1 %, respectively, P < .04). In all 37 patients, the percent decrease of FE-P was negatively correlated with blood urea nitrogen ([BUN] r = -.36, P < .05), serum creatinine (r = -.34, P < .05), and serum beta2-microglobulin (r = -.44, P < .01) and positively correlated with creatinine clearance (r = .570, P < .004), but it was not correlated with the M value or M/I ratio. These results showed that the kidneys of diabetic patients with renal insufficiency are insulin-insensitive in terms of phosphate transport, and the insulin insensitivity is related to the glomerular filtration rate but not to systemic insulin insensitivity. The percent decrease of FE-P on clamp study could be useful for assessing the insulin insensitivity of the kidney, which probably occurs primarily in the renal tubules.