<p>This study detected and analyzed the changes in the metabolomics of respiratory flora and lung lavage fluid of rats in a pneumoconiosis model. Male SD rats were randomly divided into silicon dioxide group (using SiO₂ dust, SiD), coal mine dust group (using coal mine dust, CMD) and control group (using sterile physiological saline). The changes of respiratory flora in rats were analyzed by 16S rDNA gene sequencing technology, the differential metabolites of lung lavage fluid were analyzed by non targeted metabolomics of UHPLC-Q-TOF-MS. The lung tissue structure of SiD rats was seriously damaged, and there were obvious silicon nodules. CMD rats showed a large number of cell nodules, while the alveolar structure of the control group was normal. In the upper respiratory tract, the abundance of muris and uncultured oligotrophomonas increased, while the abundance of Pasteurella, Bacteria, Rhodobacter and uncultured Rhodobacter decreased. In SiD group, the abundance of Pasteurella and Streptococcus without milk decreased. In the lower respiratory tract, the abundance of Bacteria in CMD group rats increased, and mycoplasma γ- Proteobacteria β- The abundance of proterozoic bacteria and berberidaceae decreased. In SiD group, the abundance of Bifidobacteria, Bifidobacteriaceae and Bacteria increased, β- The abundance of proterozoic bacteria and berberidaceae decreased. Among the metabolic pathways mainly involved, pyrimidine metabolism, D-glutamine and D-glutamate metabolism may be the key metabolic pathways in the development of pneumoconiosis. Dysregulation of Betaproteobacteriales, Burkholderiaceae, Bifidobacteriales, Bifidobacteriaceae, Streptococcus_agalactiae may lead to the occurrence of pyrimidine metabolism, D-glutamine and D-glutamate metabolism abnormalities in pneumoconiosis.</p>