BACKGROUND: Methicillin resistant METHODS: Evaluating the antibacterial effect of drugs through RESULT: The MIC of SH and PNC are 60-80 μg/mL and 40-70 U/mL, respectively. The FICI of the combined group is 0.375-0.5625, and the optimal drug ratio is SH20 μg/mL + PNC15u/mL. The number of central granulocytes infiltrated in the combined group was less than that in other groups, and the levels of IL-6 and TNF-α were significantly reduced. In addition, the collagen fibers in the wound were significantly increased. Thirteen target genes were predicted through network pharmacology, among which the core targets were IL1B, IL6, MMP9, IFNG, and TNF. SH and PNG have shown good binding potential with various targets in molecular docking. Among the 83 potential pathways of action, IL-17 signaling pathway is considered a key pathway for promoting wound healing. CONCLUSION: Sodium houttuyfonate combined with penicillin G can inhibit bacterial growth in MRSA infected wounds in rats, reduce neutrophil infiltration, promote collagen fiber generation in wounds, and decrease the expression levels of inflammatory factors IL-6 and TNF-α in the blood of rats after MRSA infection. It promotes wound healing through multiple targets and pathways, and preliminarily reveals the drug's targets and molecular mechanisms.