To evaluate the effect of chronic hyperinsulinemia on blood pressure in salt-dependent hypertension, we infused insulin (1.0 IU/d, n=15) or saline (n=13) for 4 weeks into deoxycorticosterone acetate-salt hypertensive rats. The insulin infusion increased plasma insulin levels to 24±2 μU/mL, which was higher than in the saline-infused rats (9±1 μU/mL) but was still within the physiological range. Blood pressure was measured by the tail-cuff method twice a week, and daily sodium intake and urinary sodium excretion were calculated for 3 weeks. At week 4, arterial pressor responsiveness to norepinephrine, angiotensin II, and hexamethonium bromide was evaluated. After 14 days of chronic infusion, the insulin group showed a higher blood pressure than the saline group (on 21st day: 178±6 versus 156±5 mm Hg, P<.05 by tail-cuff method; 171 ±4 versus 149±3 mm Hg, P<.05 by direct intraarterial measurement). This blood pressure difference was eliminated after ganglionic blockade with hexamethonium bromide (86±4 mm Hg in insulin-treated and 89±4 mm Hg in saline-treated rats by direct intra-arterial measurement). Throughout the experiment, neither sodium balance nor arterial pressor responsiveness to norepinephrine or angiotensin II differed between the two groups. In conclusion, chronic hyperinsulinemia in the physiological range augments the development of hypertension in salt-dependent hypertension, and this augmentation may be mediated by sympathetic stimulation independent of salt retention.