Despite the high rate of occurrence of both diabetes and hypertension in humans, the cardiovascular effects of the two conditions have not been investigated when they occur simultaneously. Thus this study examined the vascular effects of simultaneous type 2 diabetes and renal hypertension on endothelial function. Serum malondialdehyde and systolic blood pressure (SBP) were measured, glucose tolerance test (GTT) was performed, and concentration-response to phenylephrine (PE) in the absence and presence of nitro-l-arginine methyl ester (l-NAME), acetylcholine and sodium nitroprusside were conducted on aortic rings from diabetic control, type 2 diabetes, sham-operated, renal hypertensive, and simultaneous type 2 diabetes plus hypertension rats respectively. Hypertension, diabetes, and simultaneous diabetes and hypertension were associated with either increased or decreased maximal responses (E(max)) of PE dependent on in the presence or absence of l-NAME. There was also increased serum malondialdehyde and decreased E(max) of acetylcholine. Thus simultaneous hypertension and diabetes caused a greater decrease in E(max) of acetylcholine compared to that seen with either diabetes or hypertension alone higher than that seen in hypertension. The blood glucose during GTT was lower than that seen in diabetes groups. Thus simultaneous type 2 diabetes and the SBP was renal hypertension is associated with improved glucose tolerance, but with further deterioration of endothelial dysfunction compared with either condition alone.