The invasion of Staphylococcus aureus into respiratory epithelial cells and the followed inflammatory responses cause serious tissue damage.The aim of this study was to investigate the effects of ginsenoside Rg_1(Rg_1)on S.aureus infection in vitro and its action mechanism.An internalization model was constructed to determine the effect of Rg_1 on S.aureus invasion. The changes of expression of integrinβ1,NF-κB and glucocorticoid receptor were analyzed by Western blot.Expression of pro-inflammatory genes was validated using RT-PCR.The results demonstrated that Rg_1 treatment could reduce the invasion of S.aureus into rat pulmonary epithelial cells by down-regulating integrinβ1.Its anti-inflammatory action was exerted through reducing NF-κB and expressions of intercellular adhesion molecule-1(ICAM-1),tumor necrosis factor-α(TNF-α),interleukin-2 (IL-2)and interleukin-6(IL-6).The increased expression of glucocorticoid receptor was involved in this regulation.The results suggested that Rg_1 could play a positive role in reducing S.aureus infections.Rg_1 could be used for the treatment of S.aureus infection,potentially.