Abstract: OBJECTIVE Postpartum mice with experimental mastitis induced by Staphylococcus aureus infection were used as the model to investigate the effect of glucocorticoid on immune regulation and oxidative stress in postpartum mice. METHODS The mastitis model mice were prepared by nipple perfusion with S. aureus. Different doses of glucocorticoids were injected into the abdominal cavity to observe the health status of the mice and pathological changes of breast tissue. Body temperature, body weight, inflammatory cell classification count, and colony count were measured. IL-1β, IL-17A, TGF-β1 and TNF-α protein expression levels and oxidative stress index levels were detected. RESULTS The body temperature and body weight of mice in the model group and treatment group were significantly different from those in the control group (P<0.05). With the increase of the therapeutic dose, the number of various inflammatory cells showed a downward trend. Mice in the control group mice had complete mammary tissue structure, with no abnormal pathological changes and no inflammatory cell infiltration; mouse mammary tissues in the model and treatment groups showed various degrees of lesions, and the mammary tissues in the model group were infiltrated with a large number of inflammatory cells. The degree of lesions in the treatment group was reduced. There was very significant differences in left and right mammary indexes between the treatment group and the control group (P<0.05). The levels of the protein expression (IL-1β, IL-17A, TGF-β1, TNF-α) and oxidative stress indexes were significantly different between the model group and the treatment group, with the highest expression level in the model group and the lowest in the high-dose treatment group. CONCLUSION Glucocorticoids can regulate the immune level of mice with bacterial mastitis, and have a regulating and reversing effect on the level of oxidative stress. As the treatment dose increases, immune-related proteins and oxidative stress indicators gradually tend to normal levels.