Objective To investigate the effect of glucocorticoid on the expression of Huntingtinassociated protein 1（HAP1）in rat hypothalamus. Methods Eighty male Wistar rats were divided into 4 groups: control group (injection of 0.9% saline, n=24）, corticosterone group［(injection of corticosterone, 5mg/(kg.12h), EM>n/EM>=40］, corticosterone+ RU38486 group［con-injection of corticosterone with its receptor antagonist RU38486, 10mg/(kg.12h), EM>n/EM>=8］ and Hydrocortisone group［orally given hydrocortisone (0.01g/L）in drink water, EM>n/EM>=8］. Corticosterone group was further divided into corticosterone 1day, corticosterone 3days, corticosterone 5days and corticosterone 7days group according to the difference in time after corticosterone -injection. The expression of HAP1 was studied 3days after co-injection of corticosterone and RU38486 in corticosterone +RU38486 group. Hydrocortisone was consecutively applied in the drink water for 1 month in hydrocortisone group. RT-PCR and Western blotting were used to explore the expression of HAP1 in rat hypothalamus. Results The expression of HAP1 and the level of its mRNA were decreased significantly in hypothalamus 1day and 3days after injection of corticosterone. The expression of HAP1 began to increase 5days after injection of corticosterone and recovered to the control level 7days after injection. The mRNA of HAP1 increased markedly 5days after injection and the level was higher than that of control group. The expression of HAP1 in hypothalamus significantly decreased in hydrocortisone group. Co-injection of corticosterone with RU38486 blocked corticosterone-induced action on HAP1 expression in hypothalamus. Conclusion