This study tests the hypothesis that lipids could act as an alternative fuel source in the brain during insulin induced hypoglycemia. Male Sprague-Dawley rats were subjected to hyperinsulinemic (5 mU.kg^-1.min^-1) hypoglycemic (~50mg/dl) clamps. In protocol 1, Intralipid (IL), a fat emulsion, was infused intravenously in order to prevent the fall in free fatty acid levels that occurs in response to hyperinsulinemic hypoglycemia. Intravenous lipid infusion did not alter the counterregulatory responses to hypoglycemia. To test whether Intralipid could have central effects in mediating the counterregulatory response to hypoglycemia; in protocol 2, the brains of pre-cannulated rats were intracerebroventricularly (ICV) infused with Intralipid, or artificial cerebrospinal fluid (aCSF) as control. Unexpectedly, the epinephrine and glucagon response to hypoglycemia was significantly augmented with ICV IL infusion. To determine if central IL infusion could restore defective counterregulation; in protocol 3, rats were made recurrently hypoglycemic (RH) for three days and on the fourth day underwent hyperinsulinemic hypoglycemic clamps with ICV IL or aCSF infusion. RH rats had the expected impaired epinephrine response to hypoglycemia and ICV IL infusion again significantly augmented the epinephrine response in RH rats to normal. With regard to our experimental model of hypoglycemic counterregulation, we conclude that, 1) systemic lipid infusion did not alter the counterregulatory response to hypoglycemia, 2) the intracerebroventricular infusion of lipids markedly increased CSF FFA levels and paradoxically augmented the epinephrine and glucagon responses, and 3) the blunted sympathoadrenal response in recurrently hypoglycemic rats was completely normalized with the ICV lipid infusion. It is concluded that in the setting of insulin-induced hypoglycemia, increased brain lipids can enhance the sympathoadrenal response.