Abstract: Objective: To investigate whether manganese-induced inflammatory activation in BV2 cells is associated with mitophagy. Methods: Mouse microglia cells BV2 were exposed to different concentrations of manganese (0 μmol/L, 50 μmol/L and 100 μmol/L) for 12 h, and 1 μg/mL lipopolysaccharide (LPS) was used as a positive control group. Cell vialibility was detected by Alarmarblue assay and changes of lysosomal number and fluorescence intensity were detected by fluorescent probe; autophagic changes were observed by transmission electron microscopy; the extent of lysosomal and mitochondrial fluorescence co-localization was observed by confocal microscopy; western blotting was performed to detect the expression levels of cellular inflammatory proteins NLRP3, autophagy-related proteins (p62, LC3-II/I), and mitochondrial outer membrane protein VDAC1 after 12 h of exposure to different concentrations of manganese. Mitophagy inhibitor Bafilomycin A1 pretreatment verified the effect of manganese exposure on autophagic flow and the aforementioned inflammatory hallmarks protein expression. Results: When BV2 cells were exposed to manganese at concentrations greater than 50 μmol/L, the BV2 cell survival rate was decreased, NLRP3 expression was increased (P＜0.01), and the number of lysosomes and their co-localization with mitochondria significantly were increased (P＜0.05). The protein expression levels of VDAC1 and autophagy marker protein LC3-II/I were decreased and p62 was increased in the manganese-exposed group (P＜0.05). Bafilomycin A1 pretreatment significantly reversed the autophagy marker protein expression except p62 (P＜0.05). Conclusion: Manganese induces inflammatory activation in BV2 cells and increases mitophagy at 50-100 μmol/L exposure dose. Inhibition of mitophagy by Bafilomycin A1 can promote manganese exposure-induced inflammatory activation in BV2 cells.