Objective To investigate the in vivo pharmacodynamics of γ-PGA-DEX micelle which was prepared by loading dexamethasone（DEX）with γ-polyglutamic acid（γ-PGA）in the treatment of rheumatoid arthritis（RA）. Methods DBA/1 mice were used to establish the collagen-induced arthritis（CIA）model. On the 21st day after the first immunization，the mice were randomly grouped according to the arthritis scores，with 5 mice in each group，and γ-PGA-DEX was given by tail vein injection every 3 days ac⁃cording to the dose of each group. The joint swelling degree，weight change，joint score and histopathological examination of ankle joint were performed during each administration. In addition，the ebiosicence mouse TNF-α，IL-1βand IL-6 kits were used to determine the pro-inflammatory cytokines TNF-α，IL-1βand IL-6 in mouse serum. Results Compared with the blank group，the body weight of mice in the γ-PGA-DEX group showed an increasing trend during the treatment，and the joint index score was significantly lower than that of the free DEX treatment group，and it was the lowest in all treatment groups，showing a good therapeutic effect. HE staining of joint pathological sections demonstrated that there was no significant difference between the γ-PGA-DEX group and the normal group. Furthermore，there was no obvious inflammatory cell infiltration and bone destruction，and the pathological score was 2. Compared with the free group，the levels of TNF-α，IL-1β and IL-6 in the serum of mice in the γ-PGA-DEX group were significantly decreased（P<0.01）. Conclusion γ-PGA-DEX micelle showed good therapy effect in the treatment of RA，and it would be a nano-drug with poten⁃tial application prospect in the treatment of rheumatoid arthritis and other inflammatory diseases.