Objective: To investigate the effect of glucocorticoid (GC) to cortisol-binding globulin (CBG) expression in rats and the correlation between the changes of CBG levels and the osteonecrosis of the femoral head (ONFH) in rats after GC treatment. Methods: A total of 72 healthy adult SD rats were randomly divided into low-dose group and high-dose group by computer random grouping.Thirty-six rats of low-dose group were injected dexamethasone at a dose of 1.5 mg·kg^-1·d^-1.Thirty-six rats of high-dose group were injected dexamethasone at a dose of 3.0 mg·kg^-1·d^-1.The blood samples were regularly collected, CBG levels in blood samples were detected by Western-blotting.Rats were killed in batches, femoral head was collected and observed under light microscope after HE staining.The bone lacuna of each group was compared and the ratio of empty lacuna was calculated.Finally, the correlation between the change of CBG level and ONFH was evaluated. Results: On the first day after administration, the CBG level of the two groups decreased, and reached the lowest level on the seventh day of administration, and then gradually increased.The reduction of CBG level in the high dose group was greater.With the increase of time after treatment, the number and rate of bone lacuna void in the two groups increased gradually.28 days after treatment, the number of empty bone lacunae and the rate of empty bone lacunae in the low dose group were (6.75±0.42) and (13.98±2.19)%, respectively, which were lower than those in the high dose group[(11.03±0.62) and (21.99±3.17)%, t=4.864, 3.926, all P<0.05]. Conclusion The risk of ONFH is increased with the increase of the dose of dexamethasone, and there was no significant difference between the sexes.The decrease of serum CBG level after medication is correlated with the occurrence of ONFH.