Silicosis, one of the most ancient occupational diseases, has not been elucidated and addressed until now. Although some medicines were partly effective in the clinical treatment and certain plausible mechanisms were partially ascertained, it is still urgent and necessary to explore its real and specific pathogenesis. With the development of the cell co-culture technique, the transwell co-culture system has been applied in several scientific fields, which is able to simulate the pathogenic process in vivo to the largest extent. In this sense, a transwell co-culture cell model for silicosis including RFL-6 (lung fibroblasts of rats), RLE-6TN (type II alveolar epithelial cells of rats) and NR8383 (alveolar macrophages of rats) cells was successfully established and the developmental process of silicosis in this model could be roughly divided into three stages: inflammatory stage, progressive stage and fibrotic stage, as evidenced by the morphological features and the inflammatory cytokines and fibrotic proteins of supernatants and the cells in this system. Results of this project will pave the way for clarifying the mechanism of silicosis and building a practical platform for the further exploration of molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis.