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.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.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.Zhike Erfang can alleviate pneumonia caused by MRSA by inhibiting TRAF6 and inducing NLRP3 inflammatory body activation.© 2025 Zhang et al.