Cocaine- and amphetamine-regulated transcript (CART) has been implicated in the feeding behavior and the regulation of hypothalamic-pituitary-adrenal axis activity. In this study we investigated the expression of CART mRNA in the hypothalamus at several intervals after adrenalectomy or sham surgery in basal conditions or after a fasting-refeeding regimen. Male Wistar rats, with free access to food and drinking, were subjected to bilateral adrenalectomy (ADX) or sham surgery. Plasma corticosterone, ACTH, and leptin levels, epididymal and perirenal fat content, and CART expression were determined 1, 3, 7 and 14 days after surgery. Another set of rats was subjected to a 48-h fasting period followed by refeeding during 4 h on the 7th day after ADX or sham surgery. On the day of the experiment, rats were anesthetized and perfused and the brain was processed for CART mRNA in situ hybridization. We observed that long-term but not short-term adrenalectomy decreased leptin plasma levels and CART expression in the arcuate and paraventricular nuclei. Furthermore, we showed that CART expression was reduced by fasting and it was increased after refeeding in the sham group, however, CART expression was not changed by fasting or refeeding after ADX. In conclusion, the present data indicate that following long-term ADX, under freely feeding conditions, there is a decrease of CART expression in the hypothalamus that is associated with a decrease of leptin secretion. CART expression induced by feeding seems to be modulated by glucocorticoid.