The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation, endothelial function, and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes. Thirty-eight subjects with type 2 diabetes (D: age, 54 +/- 10 years, mean +/- SD, 24 men) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance (IGT) (relatives [R]: age 46 +/- 11 years, 4 men) were included. Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach) and 1% sodium nitroprusside (SNP), and ultrasound was used to measure the flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) in the brachial artery. Renal oxygenation was assessed by magnetic resonance imaging (MRI) before and during water diuresis. A decrease in the magnetic parameter R2* implies an increase in oxygenation. Renal medullary oxygenation did not improve with diuresis in either group (D: -0.5 +/- 1.9, R: -0.4 +/- 2.1, P = not significant [NS]). The renal cortical oxygenation showed a small, but statistically significant, improvement after diuresis in the 2 groups (D: -0.6 +/- 1.1, R: -0.5 +/- 0.5, P <.05). There were no correlations between the change in cortical R2* (R2* post-minus R2* prewater diuresis) and the micro- and macrovascular reactivity. The postdiuresis renal cortical R2* was negatively correlated with both the Ach- and SNP-induced skin vasodilation (% change over baseline)(r = -.40, P <.01 and r = -.39, P <.05, respectively), while no correlation existed with the FMD and NID. The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation (r = -.36, P <.05) and positively correlated with the fasting plasma glucose, total cholesterol, and vascular cell adhesion molecule (VCAM) concentrations (r =.34, P <.05, r =.31, P <.05 and r =.37, P <.05, respectively). These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity, glycemia, and lipidemia. Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes.