Objective: To investigate potential roles of miR-149 in the pathogenesis of silica-induced pulmonary fibrosis.Methods: The expression of miR-149 and inflammatory cytokine IL-6 in the lung tissues of mice with silica-induced pulmonary fibrosis was tested by Real-time PCR,Immunohistochemistry and Western blot assay.Cell lines (A549 and HBE) were used to clarify the associations among miR149, IL-6 and silica exposure by intervening miR-149 expression.The expression of IL-6 and miR-149 in cells was tested by Western blot and Real-time PCR.Results: (1) The expression of miR-149 in lung tissues of mice was down-regulated significantly, while IL-6 expression was up-regulated obviously after treatment in 1, 2 and 4 weeks.(2) Epithelial cells (A549 and HBE) were stimulated by SiO2, which could increase the cells apoptosis, and up-regulate IL-6 expression obviously.After HBE cells and A549 cells were stimulated by SiO2 in 12 hours and 24 hours, respectively, the expression of miR-149 was down-regulated significantly (P < 0.001) in HBE cells and the same trend in A549 cells.Dysregulated expression of miR-149 in vitro influenced the IL-6 expression in A549 cells.High expression of miR-149 attenuated IL-6 expression, adverse results were found after miR-149 was inhibited.Conclusion: (1) Down-regulation of miR-149 and up-regulation of IL-6 may involve in the progress of silica-induced pulmonary fibrosis;(2).miR-149 may regulate IL-6 expression in A549 cells negatively.Further studies are needed to reveal their dynamic changes in the pathogenesis of pneumoconiosis.