Endogenous endothelin action is augmented in human obesity and type 2 diabetes, and contributes to endothelial dysfunction and impairs insulin-mediated vasodilation in humans. We hypothesized that insulin resistance-associated hyperinsulinemia could preferentially drive endothelin-mediated vasoconstriction. We applied hyperinsulinemic euglycemic clamps with higher insulin dosing in obese subjects than lean subjects (30 versus 10 mU/m²/min, respectively), with the goal of matching insulin's nitric oxide-mediated vascular effects. We predicted that under these circumstances insulin-stimulated ET-1 action (assessed with the type A endothelin receptor antagonist BQ123) would be augmented in proportion to hyperinsulinemia. Nitric oxide (NO) bioactivity was assessed using the nitric oxide synthase inhibitor L-NMMA. Insulin-mediated vasodilation and insulin-stimulated NO bioavailability were well matched across groups by this approach. As expected, steady state insulin levels were ~3 fold higher in obese than lean subjects (109.2±10.2 pmol/L versus 518.4±84.0, p=0.03). Despite this, the augmentation of insulin-mediated vasodilation by BQ123 was not different between groups. ET-1 flux across the leg was not augmented by insulin alone, but was increased with the addition of BQ123 to insulin (p=0.01 BQ123 effect, p=NS comparing groups). Endothelin antagonism augmented insulin-stimulated NO bioavailability and NOx flux, but not differently between groups and not proportional to hyperinsulinemia. These findings do not support the hypothesis that insulin resistance-associated hyperinsulinemia preferentially drives endothelin-mediated vasoconstriction.