Abstract: Objective: To investigate the effect of glucocorticoid on expression of hypothalamic Agouti-related peptide(AGRP),and cocaine and amphetamine regulated transcript(CART) in normal and obese rats.Methods: Both normal and obese SD rats were randomly assigned to 3 groups:normal salina group(NSG),low dose glucocorticoid group(LDG) and high dose glucocorticoid group(HDG),and intraperitoneal injection with normal saline 0.2 ml/100 g,hydrocortisone sodium succinate 5 mg/kg and 15 mg/kg for 20 days.Real-time RT-PCR was used to measure the expression of AGRP,CART mRNA in hypothalamus.Results: After high dose glucocorticoid injection,the mRNA expressions of orexigenic neuropeptide AGRP and anorexigenic neuropeptide CART,were significantly lower than the NSG in hypothalamus of both obese and normal rats(P<0.05).After low dose glucocorticoid injection,there were no differences of hypothalamic AGRP,CART mRNA expressions from the NSG in obese rats.In normal rats,the expressions of AGRP mRNA were significantly lower than those of the NSG after low dose glucocorticoid injection(P<0.05) while no difference of CART mRNA from the NSG.Conclusions: High dose glucocorticoid downregulated orexigenic neuropeptide AGRP and anorexigenic neuropeptide CART mRNA expression levels in hypothalamus of obese and normal rats.Low dose glucocorticoid downregulated orexigenic neuropeptide AGRP mRNA expression in hypothalamus of normal rats.