〔Abstract〕 Objective To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll-like receptor 4(TLR4)/nucleotide-binding oligomerization domain-containing 3(NLRP3) pathway in rats with chronic obstructive pulmonary disease (COPD). Methods Thirty-six male SD rats were selected and randomly divided into four groups: the normal control group, the model group, the prednisone treatment group, and the ginkgo biloba extract treatment group, with 9 rats in each group. Except for the normal control group, the COPD rat models in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with cigarette smoke exposure. After successful modeling, the rats were continuously administered drugs for 12 weeks, followed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin-eosin (HE) staining technique; the mRNA and protein expression levels of TLR4, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and NLRP3 in rat lung tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. Results Compared with the normal control group, the lung tissues of rats in the model group were significantly damaged, and the protein and mRNA expression of TLR4, TNF-α, IL-1β, and NLRP3 increased ( P < 0.05). Compared with the model group, lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group, and TLR4, TNF-α, IL-1β, NLRP3 protein and mRNA expression decreased ( P < 0.05). Conclusion Ginkgo biloba extract may reduce TLR4, TNF-α, IL-1β, and NLRP3 expression in lung tissues of COPD rats and alleviate their airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.