Objective To investigate the expression of matrix metalloproteinase 3 (MMP3) in a mouse silicosis model induced by SiO₂, and explore its role in pulmonary fibrosis. Methods Six male C57B/6 mice were randomly divided into control and silicosis groups (n=3). The silicosis model was established via intratracheal instillation of SiO₂ suspension (0.2 g/kg); the control group were intratracheally instilled with the same amount of normal saline. Human pulmonary fibroblasts (HPF-a) and mouse lung fibroblasts (MLg) were treated with 5 ng/ml of transforming growth factor-β₁ (TGF-β₁) to construct an ex vivo silicosis cell model. Masson trichrome and Sirius red staining were used to assess the effects of SiO₂ on pulmonary tissue and extracellular matrix (ECM) deposition. Single-cell transcriptomics was performed on mouse lung tissue, with bioinformatics analyses identifying ECM-associated cellular composition changes and key genes. The expression and distribution of these key genes were analyzed by spatial transcriptomics. Western blotting was employed to detect Vimentin and MMP3 protein levels in mouse lung tissue and fibroblasts. Immunofluorescence staining was used to localize MMP3 in lung ECM and TGF-‍β₁-treated fibroblasts and to evaluate its accumulation in the ECM. Results Masson's and Sirius red staining revealed fibrotic changes and significant ECM collagen deposition in mice of silicosis group. Single-cell and spatial transcriptomics identified fibroblast-associated alterations in ECM components, with MMP3 emerging as a key gene. MMP3 mRNA expression was significantly elevated in mouse lungs of silicosis group and was localized primarily to fibrotic lesions. Western blotting showed a significant increase in MMP3 protein levels in the lungs of silicosis group mice compared to control group (P<0.05). TGF-‍β₁ treatment led to a time-dependent increase in MMP3 protein levels in HPF-a cells (P<0.05). Immunofluorescence revealed elevated MMP3 expression in the ECM of mouse lungs in silicosis group (P<0.05). When TGF-‍β₁ treated MLg cells were seeded onto normal mouse lung ECM, MMP3 expression increased (P<0.05). Similarly, after decellularizing ECM seeded with MLg cells, MMP3 expression levels remained significantly elevated (P<0.01). Co-localization analysis showed enhanced Vimentin and MMP3 signals in and around silicotic nodules in mice of silicosis group (P<0.01). Conclusions In the mouse silicosis model, secretion of MMP3 from fibroblasts increased with TGF‑β₁ treatment, accumulating in the pulmonary ECM, exacerbating collagen deposition, and promoting fibrosis. MMP3 may serve as a potential therapeutic target for silicosis-induced pulmonary fibrosis.