We previously showed, through direct neural recording in conscious rats, that hypoglycemia increases adrenal sympathetic nerve activity (SNA) both acutely and 24 hours following the second of 2 daily antecedent hypoglycemic episodes. Nonetheless, antecedent hypoglycemia impaired catecholamine responsiveness to subsequent acute hypoglycemia. Here we hypothesized that antecedent, nonhypoglycemic adrenal sympathetic stimulation by leptin would impair acute adrenal catecholamine responsiveness to subsequent hypoglycemia. We also hypothesized that acute leptin administration (after 2 days of antecedent hypoglycemia) would enhance adrenal SNA and thereby enhance catecholamine responsiveness to concurrent hypoglycemia. Leptin or saline was administered to normal rats in repeated subcutaneous injections for 2 days prior to acute insulin-induced hypoglycemia. In contrast to our hypothesis, antecedent leptin did not change catecholamine responsiveness or glycemic change in response to subsequent acute insulin administration. In additional studies, intravenous leptin or saline was acutely administered beginning 1 hour before insulin-induced hypoglycemia. All rats had been exposed to antecedent hypoglycemia. In these experiments, acute leptin did not alter catecholamine responses to insulin or glycemic change during or after termination of insulin. We conclude that antecedent nonhypoglycemic sympathetic stimulation by leptin does not alter subsequent catecholamine or glycemic responses to insulin. Moreover, concurrent leptin does not enhance catecholamine responses to insulin in rats exposed to antecedent hypoglycemia.