Abstract: Objective: To investigate the effect of meropenem(MEP) on airway remodeling in rats with chronic obstructive pulmonary disease(COPD) and its regulatory effect on JAK2-STAT3-RORyt signaling pathway.Methods: Forty rats were randomly divided into control group, COPD group, COPD+MEP group and JAK2 inhibitor group, with 10 rats in each group. Except for the control group, the COPD rat model was reproduced in the other groups. After establishing the model, the COPD+MEP group received an intramuscular injection of 20mg/kg MEP into the gluteal muscle, while the JAK2 inhibitor group received an intramuscular injection of 8 mg/kg AG490 into the gluteal muscle. The ratio of forced vital capacity(FVC) to forced expiratory volume in 0.3 second(FEV_0.3) in each group was compared. Hematoxylin-eosin(HE) staining was used to observe the pathomorphological changes of lung tissue. The number of total cells, neutrophils, lymphocytes and macrophages in bronchoalveolar lavage fluid(BALF) was analyzed. The contents of interleukin(IL)-6, IL-8, tumor necrosis factor(TNF)-α and IL-1β in lung tissue were determined by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of transforming growth factor-β1(TGF-β1), collagen Ⅰ, α-smooth muscle actin(α-SMA), JAK2, STAT3 and RORyt was detected by real-time fluorescence quantitative PCR(RT-qPCR) and western blotting, respectively. Results:Compared with the control group, the body weight and FEV_0.3/FVC of the COPD group were decreased, the mRNA and protein expression levels of collagen Ⅰ, α-SMA, TGF-β1, JAK2, STAT3 and RORyt were increased, and the number of total cells, macrophages, neutrophils and lymphocytes in BALF was increased. The contents of IL-8, IL-6, TNF-α and TGF-β1 in lung tissue were increased(all P<0.05). HE staining showed that the airway mucosal folds were increased and prolonged, a large number of inflammatory cells clustered around the trachea and blood vessels, and the smooth muscle thickened in the COPD group. Compared with the COPD group, the COPD+MEP group and the JAK2 inhibitor group had lower mRNA and protein expression levels of JAK2, STAT3 and RORyt, and a lower number of total cells, macrophages, neutrophils and lymphocytes in BALF. The contents of IL-8, IL-6, TNF-α and TGF-β1 in lung tissue were decreased(all P<0.01). Conclusion: MEP can alleviate airway remodeling in COPD rats by inhibiting JAK2-STAT3-RORyt signaling pathway and pulmonary inflammation.