Objective: This study aimed to investigate the differential therapeutic effects of XuanFei HuaZhuo Pill (XFHZP) on rat pneumonia models with syndrome (Damp-Heat pneumonia, DH) and elucidate its underlying mechanisms using proteomics, providing experimental evidence for traditional Chinese medicine (TCM) in pneumonia treatment. Methods: DH rat models were established. Therapeutic effects were evaluated via: clinical signs and scores (general condition, tongue/ear/claw color, urine/stool characteristics); lung index; histopathology (HE staining); ELISA for pulmonary IL-6 and TNF-α levels; hematology (WBC, Gran, Mon, MPV); pulmonary function (respiratory frequency [F], minute ventilation [MV]). Astral DIA quantitative proteomics was performed on the right inferior lung lobes of CON, DH, and XFHZP+DH groups to identify differentially expressed proteins (DEPs) between CON-DH and DH-XFHZP+DH groups. Key DEPs (e.g., ROCK1, MKNK1) were further verified by immunohistochemistry (IHC) and Western blot (WB), including their downstream targets (phospho-MLC2, phospho-eIF4E). Results: Compared to CON, DH rats exhibited hyperactive behavior, red tongues, ear vessel dilation, yellow urine, and sticky stools.And displayed elevated lung indices, alveolar wall thickening, inflammatory infiltration, and capillary congestion (HE staining), alongside increased IL-6/TNF-α (p < 0.05), WBC/Gran/Mon/MPV/F (p < 0.05), and reduced MV (p < 0.05). XFHZP treatment in DH rats (XFHZP+DH) significantly ameliorated lung pathology, reduced IL-6/TNF-α, and normalized WBC/Gran/Mon/MPV/F/MV (all p < 0.05). Proteomics identified 1348 DEPs in CON-DH and 448 in DH-XFHZP+DH, including AAK1, CACNA2D1, EIF4E, HSD11B1, ROCK1, and TDP1. KEGG analysis highlighted cGMP-PKG and insulin signaling pathways as potential mechanisms for XFHZP in DH pneumonia. IHC and WB revealed upregulated ROCK1/MKNK1 in DH lungs, accompanied by increased MLC2/eIF4E phosphorylation, which were suppressed by XFHZP. Conclusion: XFHZP exerts significant therapeutic effects on DH-type pneumonia, likely by downregulating ROCK1/MKNK1 expression, inhibiting MLC2/eIF4E phosphorylation, relaxing airway smooth muscle, and attenuating inflammation. This study provides molecular-level evidence for XFHZP’s efficacy and offers novel insights into TCM-based pneumonia treatment.