PURPOSE: The therapeutic effects of Zhike Erfang in modulating the cellular responses and immune microenvironment associated with MRSA-induced acute lung injury remain unclear. This study aims to elucidate the potential mechanisms by which Zhike Erfang mitigate the cellular and molecular effects of MRSA in a laboratory model. PATIENTS AND METHODS: A mouse model of acute lung injury was established using heat-inactivated MRSA. Lung tissue and bronchoalveolar lavage fluid were collected for analysis. Macrophages were pretreated with Zhike Erfang for 30 minutes before exposure to heat-inactivated MRSA for 24 hours. Protein expressions of TRAF6, iNOS, TNF-α, IL-1β, NLRP3, and caspase-1 in lung tissues were quantified using Western blot. The content of LDH was detected by the lactate dehydrogenase cytotoxicity test kit. RESULTS: Zhike Erfang significantly reduced the expression of iNOS, LDH, TNF-α, IL-1β, NLRP3, and caspase-1 in a dose-dependent manner in lung tissues from the MRSA model. Zhike Erfang inhibited the expression of TRAF6. CONCLUSION: Zhike Erfang can alleviate pneumonia caused by MRSA by inhibiting TRAF6 and inducing NLRP3 inflammatory body activation.