[ Abstract ] Objective To investigate the operational dynamics through which the Xuanfei Jiedu Formula ameliorates pulmonary damage in rats afflicted with Multidrug Resistant Pseudomonas Aeruginosa (MDR-PA) pneumonia, by modulating the activity of the IKK/NF-κB signal transduction cascade. Methods Eighty-four rats were randomly divided into 7 groups : Control group, Model group, XFJDF-low dose group, XFJDF-medium dose group, XFJDF-high dose group, Imipenem ( IPM ) group and Pyrrolidinedithiocarbamate ammonium ( PDTC ) group. 12 in each group. The MDR-PA pneumonia rat model was established by oral tracheal intubation. After the model was successfully constructed, the rats in the low, medium and high dose Xuanfei Jiedu Decoction groups were given the corresponding dose of drugs by gavage, the rats in the imipenem cilastatin group were given intraperitoneal injection of IPM, while the rats in the control group and the model group were given the same volume of normal saline by gavage, twice a day for 7 days. PDTC was intraperitoneally injected at 1 h before model establishment, 12 h and 24 h after model establishment in NF-κB inhibitor group. The behavior status, body weight change, spleen and thymus index, lung wet weight / lung dry weight ratio of rats were observed. The pathological changes of lung tissue were evaluated by HE staining. TUNEL staining was used to detect the apoptosis of lung tissue cells. The levels of IL-1β, TNF-α, TGF-β and IL-10 in serum were detected by ELISA. The contents of GSH and MDA, MPO activity and total antioxidant capacity ( T-AOC ) in serum of rats were determined by colorimetry and TBA method. The expression of NF-κBp65 in lung tissue was detected by immunohistochemistry. The expression of IKKβ and NF-κBp65 mRNA in lung tissue was analyzed by PCR. The expression levels of IKKβ, p-IKKβ, NF-κBp65 and p-NF-κBp65 in lung tissue were measured by Western Blot. Results Compared with the Control group, the rats in the Model group had reduced diet, lack of luster in hair, slow response, reduced activity, accelerated respiratory rate, accompanied by murmurs, and significantly reduced body weight ( P < 0.01 ). Marked enhancements were observed in both the spleen and thymus indices (P < 0.01). The lung wet weight / lung dry weight ratio exhibited a substantial rise (P < 0.01), concurrently with an augmentation of alveolar secretions in lung tissue. Infiltration of abundant inflammatory cells was noted, alongside a notable escalation in lung tissue apoptosis. Serum concentrations of IL-1β, TNF-α, TGF-β, and IL-10 demonstrated a substantial upsurge (P < 0.01), alongside an augmented MDA content and heightened MPO activity (P < 0.01). Conversely, GSH levels and T-AOC capabilities displayed a notable decline (P < 0.01). In the lung tissue, there was a remarkable elevation in the expression of IKKβ and NF-κB p65 mRNA (P < 0.01). Furthermore, the ratios of p-IKKβ/IKKβ and p-NF-κBp65/NF-κBp65 in the lung tissue also showed a significant rise (P < 0.01).Compared with the Model group, the treatment group could improve the above indicators to varying degrees ( P < 0.05, P < 0.01 ), among which the Xuanfei Jiedu Formula high-dose group and the IPM group were more significant. Conclusion Xuanfei Jiedu Formula may improve lung injury in rats with MDR-PA pneumonia by inhibiting IKK / NF-κB signaling pathway.