Orexin/hypocretin is indicated to affect various physiological functions and behaviors, such as energy balance, feeding, wake-sleep cycle, stress response, and reproduction. This study investigated postnatal development and aging changes of the orexin neuron in the male rat hypothalamus. The brain tissue of rats from I week to 24 months old was analyzed by immunohistochemistry for two forms of orexin peptides, orexin-A and -B. The number of immunoreactive cells for each age group was counted and the immunoreactive intensity was also analyzed in order to reveal the changes in the number of expressing cells and the relative amount of the peptides. The number of orexin immunoreactive cells increased from postnatal 2 weeks to maturation, then slightly decreased and stabilized until the age of 8 months old, but it was significantly decreased by 24 months old. The intensity of the immunoreaction followed almost the same pattern. Our findings demonstrate that orexin neurons are increased during maturation and then are significantly decreased during the period from 8 to 24 months old, indicating an involvement of orexin in the physiological changes in rat aging such as energy balance, sleep, stress response, and reproduction. (C) 2009 Elsevier Ireland Ltd. All rights reserved.