Objective To investigate the changes of hypothalamic-pituitary-adrenal (HPA) axis secretory function in male and female castrated rats, and to confirm that sex hormones can affect the function of HPA axis and explore if this effect has relationship with gender and the lasting of time.Method Eighty SPF SD rats (half male and female) aged 8 weeks, body weight 180-220 g, were randomly divided into the male model group, male control group, female model group and female control group, 20 rats in each group. After one week adaptation feeding, rats in the male and female model groups were castrated. At 3 and 13 weeks after castration, blood samples were collected from the heart apex, and serum content of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) were assayed by using enzyme-linked immunosorbent assay (ELISA) and statistically analyzed. Results At 3 weeks after castration, the serum contents of CRH and CORT in the male model group were significantly lower than those in the male control group (P<0.01), and serum ACTH level in the male model group was significantly lower than that in the male control group (P<0.05). In the female model group, the serum contents of CRH and CORT were lower than those in the female control group (P<0.05), and the level of serum ACTH showed a decreasing tendency. At 13 weeks after castration, serum CORT level in the male model group was significantly lower than that in the male control group (P<0.01), while other hormones showed no obvious changes. The serum CORT content in the female model group was lower than that in the female control group (P<0.05), while other hormones changed not obviously. At 13 weeks after modeling, compared with that at 3 weeks after castration, serum CRH, ACTH and CORT contents had no significant differences compared with those in the male and female model groups (P>0.05). Conclusions Castration causes dysfunction of the HPA axis, and this influence exits in both male and female rats. The effect of androgen on male rats is greater than that of estrogen on female rats. Castration can cause a drop of peripheral blood CRH, ACTH and CORT levels. Presumably, androgen may be more conducive to secretion of CRH, ACTH and CORT than that on females. In the condition of low sex hormone levels, the secretion of these three hormones are not changed correlating with the week's growth of the rats.