Objectives: The aim of the paper is to explore the role of lung microbiome disorder in lung tissue injury induced by exposure to particulate matter with a maximum diameter of 2.5 μm (PM2.5) and the alleviation effect of Auricularia auricular-judae polysaccharide (AAP). Material and Methods: Sprague Dawley rats were given PM_2.5 suspension at a dose of 20 mg/l twice a week for 8 weeks. Then, 100 mg/kg or 200 mg/kg of AAP was administered to the rats after PM_2.5 exposure. The bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at the end of the experiment. The BALF was meant to detect changes in lung microbiome by 16S sequences and cluster analysis, with the application of the principal component analysis and the partial least squares discriminant analysis. The levels of interferon-γ (IFN-γ), and interleukin (IL)-4, IL-8, and IL-10 in lung tissue were detected by the enzyme-linked immunosorbent assay method. The pathological changes in lung tissue were observed by hematoxylin and eosin staining. Results: After PM_2.5 exposure, the alveolar septum was widened, and the structures of alveolar walls were destroyed. There was inflammatory cells infiltration in the alveolar space and the interstitial space. Alpha diversity in BALF showed that the Chao1, ACE, Simpson, and Shannon values were increased, and the lung microbiome analysis revealed that the relative abundance of Firmicutes and Clostridium increased, while the relative abundance of Bacteroidetes and Akkermansia decreased. The contents of IFN-γ and IL-8 in lung tissue increased while the content of IL-10 decreased. After the administration of AAP, the alveolar structure damage was alleviated, and the interstitial hemorrhage, edema, and inflammatory cells infiltration were reduced. The Chao1 and ACE values decreased, and the taxonomic abundance values of Akkermansia were much higher. Simultaneously, the contents of IFN-γ, IL-4, and IL-8 decreased, and the content of IL-10 increased. Conclusions: It was found that PM_2.5 resulted in lung microbiome disorder, which might lead to the inflammation of lung tissue. It was also revealed that AAP could alleviate the inflammatory damage of lung tissue induced by PM_2.5. Int J Occup Med Environ Health. 2022;35(6):651–64