Neurotrophins are important regulators in the embryogenesis, development and functioning of nervous systems. In addition to the efficacy of brain-derived neurotrophic factor (BDNF) in neurological disorders, we have found that BDNF demonstrates endocrinological functions and reduces food intake and blood glucose concentration in rodent obese diabetic models, such as C57BL/KsJ-db/db mice. The hypoglycemic effect of BDNF was found to be stronger in younger db/db mice with hyperinsulinemia than in older mice. While BDNF itself did not alter blood glucose in normal mice and streptozotocin (STZ)-treated mice, BDNF enhanced the hypoglycemic effect of insulin in STZ-treated mice. These data indicate that BDNF needs endogenous or exogenous insulin to show hypoglycemic action. In addition, BDNF treatment enhanced energy expenditure in db/db mice. The efficacy of BDNF in regulating glucose and energy metabolism was reproduced through intracerebroventricular administration, suggesting that BDNF acted directly on the hypothalamus, the autonomic center of the brain. Copyright © 2002 John Wiley & Sons, Ltd.