Objective To investigate the differential therapeutic effects of XuanFei HuaZhuo pill (XFHZP) on rat pneumonia models with damp-heat pneumonia (DH) syndrome, and to elucidate the underlying mechanisms using proteomics, to provide experimental evidence for the use of traditional Chinese medicine ( TCM) in the treatment of pneumonia. Methods A DH group model was established. Therapeutic effects were evaluated via clinical signs and scores ( general information, tongue, ear, claw nail, urine, feces), lung index, histopathology (hematoxylin-eosin), enzyme-linked immunosorbent assay for pulmonary interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels, hematology ( white blood cell count ( WBC), granulocytes ( Gran), monocytes ( Mon), mean platelet volume (MPV)), and pulmonary function ( respiratory frequency (F), minute ventilation (MV)). Astral data-independent acquisition quantitative proteomics was performed on the right inferior lung lobes from control (CON) group, DH group, and XFHZP + DH group to identify differentially expressed proteins (DEPs) between CON vs. DH and DH vs. XFHZP + DH groups. Key DEPs were verified by immunohistochemistry and Western Blot, including their downstream targets ( phospho-MLC2, phospho-eIF4E). Results Compared with CON group, DH group exhibited hyperactive behavior, red tongues, ear-vessel dilation, yellow urine, and sticky feces, and displayed elevated lung indices, alveolar wall thickening, inflammatory infiltration, and capillary congestion, plus increased IL-6 and TNF-α (P<0. 05), WBC, Gran, Mon, MPV, F (P<0. 05), and reduced MV ( P<0. 05). XFHZP treatment significanly ameliorated lung pathology, reduiced IL-6、TNF-α (P<0. 05), and nomalized WBC、 Gran、Mon、 MPV、 F (P<0. 05), MV (P<0. 05) in DH rats (XFHZP + DH). Proteomics identified 1348 DEPs in the CON vs. DH and 448 in the DH vs. XFHZP + DH group, including AAK1、CACNα2δ1、eIF4E、HSD11β1、ROCK1、TDP1. KEGG analysis highlighted cGMP-dependent protein kinase G and insulin-signaling pathways as potential mechanisms for XFHZP in DH pneumonia. ROCK1 / MKNK1 was upregulated in DH lungs, accompanied by increased MLC2 / eIF4E phosphorylation, which were suppressed by XFHZP. Conclusions XFHZP exerts significant therapeutic effects on DH syndrome 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.