【Abstract】Objective: To investigate the effects of carnosol on pulmonary inflammation and fibrosis in a murine model of chronic obstructive pulmonary disease (COPD) and to elucidate whether these effects are mediated through the regulation of TAK1 activity, thereby providing experimental evidence for targeted COPD therapy. Methods: Thirty male C57BL/6 mice were randomLy allocated into five groups (n=6 per group): normal control, COPD model, low-dose carno-sol (2.5 mg/kg), high-dose carnosol (5 mg/kg), and dexamethasone positive control (1 mg/kg). The COPD model was es-tablished through intratracheal lipopolysaccharide (LPS) instillation combined with cigarette smoke exposure and intraper-itoneal injection of cigarette smoke extract (CSE). Modeling was accompanied by drug intervention, which was adminis-tered over a consecutive 7 - day period. Twenty-four hours following the final administration, serum, bronchoalveolar lav-age fluid (BALF), and lung tissues were collected. Hematoxylin-eosin (HE) staining was performed to evaluate pulmonary histopathological changes, while Masson's trichrome staining was utilized to assess collagen deposition. Serum and BALF levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were quantified by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was conducted to determine the protein expression levels of phosphorylated TAK1 (p-TAK1), phosphorylated P38 (p-P38), phosphorylated P65 (p-P65), phosphorylated c-Jun N-terminal kinase (p-JNK), and inhibitor of NF-κB α (IκBα) in lung tissues. Real-time quantitative polymerase chain reaction (RT-qPCR) was em-ployed to measure TAK1 mRNA expression. Results: Compared with the normal control group, the COPD model group exhibited severe pulmonary histopathological damage characterized by massive inflammatory cell infiltration and substan-tial collagen fiber deposition，and an increase in mean linear intercept (MLI) (P<0.001). Serum and BALF levels of TNF-α and IL-1β were significantly elevated (P<0.001). Furthermore, the protein expression levels of p-TAK1, p-P38, p-P65, and p-JNK, along with the TAK1 mRNA expression in lung tissues, were significantly upregulated (P < 0.001). Meanwhile, the IκBα protein expression was notably down - regulated (P < 0.001). Carnosol treatment dose-dependently ameliorated pul-monary histopathological alterations, reduced inflammatory cell infiltration and collagen deposition, shortened MLI, de-creased pro-inflammatory cytokine levels, and suppressed TAK1 activity along with downstream NF-κB/MAPK pathway activation. Notably, the therapeutic efficacy of high-dose carnosol was comparable to that of dexamethasone (P>0.05). Conclusion: Carnosol dose-dependently attenuates pulmonary inflammation and fibrosis in COPD mice by inhibiting TAK1 transcription and phosphorylation, consequently blocking the downstream NF-κB/MAPK signaling cascade and ameliorating pulmonary histopathological damage. These findings suggest that carnosol may represent a potential thera-peutic agent for COPD management.