Insulin stimulates the renin-angiotensin system and induces renal vasodilation. The relationship between these opposing influences of insulin on renal vascular tone has not been explored. A hyperinsulinemic euglycemic clamp and sham insulin clamp each of 270 min duration were performed in 15 healthy individuals during high sodium balance. An angiotensin receptor blocker was administered at time 180 min. Renal plasma flow and plasma renin activity were measured serially. The response to insulin or sham insulin infusion was defined as the change from time 0 to 180 min; the response to angiotensin receptor blockade (ARB) was defined as the change from time 180 to 270 min. Insulin infusion increased plasma renin activity (P < 0.01) and renal plasma flow (P < 0.01); the latter effect plateaued by time 150 min. ARB caused a greater vasodilator response during insulin infusion compared with during sham insulin infusion (P = 0.02). Increasing renin response to insulin predicted blunting of the renal vasodilator response to insulin infusion (R(2) = 0.36, P = 0.02) and sensitizing of the renal vasodilator response to ARB during insulin infusion (R(2) = 0.59, P < 0.01). Insulin-induced activation of the renin-angiotensin system modulates insulin-induced renal vasodilation in healthy individuals. Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease.