Hyperinsulinemia has been associated with increased sympathetic nervous activity. However, direct injection of insulin into the hypothalamus of anesthetized rats produces sympatho-inhibition. This discrepancy could be due to confounding effects of anesthesia or insulin resistance on central neural function. The effect of injecting saline or insulin (3.0 or 30 mU) into the ventromedial hypothalamus on mean arterial pressure, heart rate, and renal nerve activity (RNA) was investigated in conscious rats and in rats anesthetized with urethan or pentobarbital. Insulin decreased RNA in conscious rats but had no effect in pentobarbital-anesthetized rats. In urethan-anesthetized rats with hyperglycemia, the insulin increased RNA. Drinking a 10% sucrose solution enhanced the sympathoexcitatory effect of insulin in the urethan-anesthetized rats but had no effect in the other two groups. The sucrose solution did not affect insulin sensitivity in any group; however, urethan anesthesia did produce insulin resistance. These data show that central effects of insulin are sensitive to anesthesia and do not support a sympathoexcitatory role for insulin in the ventromedial hypothalamus of conscious rats, at least in relation to the renal sympathetic nerves.