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Silica particles are commonly encountered in natural and industrial activities. Long-term environmental exposure to silica can result in silicosis, which is characterized by chronic inflammation and abnormal tissue repair in lung. To uncover the role of m6A modification in silica-induced pulmonary inflammation, we conducted this study using established mouse and macrophage models. In this study, the aerodynamic diameter of silica particles was approximately 1–2 µm. We demonstrated that silica exposure in mice caused pulmonary inflammation and increased global m6A modification levels, the downregulation of alkB homolog 5 (ALKBH5) might contribute to this alteration. Besides, we found that F4/80, a macrophage-specific biomarker, was co-expressed with ALKBH5 through dual immunofluorescent staining. In vitro studies using MeRIP assays suggested that Slamf7 was a target gene regulated by m6A modification, and specific inhibition of ALKBH5 increased Slamf7 expression. Mechanistically, ALKBH5 promoted m6A modification of Slamf7, which decreased Slamf7 mRNA stability in an m6A-dependent manner, ultimately regulating Slamf7 expression. In addition, silica exposure activated PI3K/AKT and induced macrophage autophagy. Inhibition of Slamf7 promoted autophagy, reduced the secretion of pro-inflammatory cytokines, and improved silica-induced pulmonary inflammation. In summary, ALKBH5 can regulate silica-induced pulmonary inflammation by modulating Slamf7 m6A modification and affecting the function of macrophage autophagy. [Display omitted] • Silica-caused pulmonary inflammation was accompanied by increased m6A modification. • ALKBH5 regulated the alteration of m6A modification induced by silica exposure. • Slamf7 was a target gene in silica-induced inflammation modulated by ALKBH5. • Macrophage autophagy regulated by Slamf7 was associated with pulmonary inflammation. [ABSTRACT FROM AUTHOR]