Objective To investigate the effect of methyltransferase-like 3 ( METTL3)-mediated N6 methyladenosine (m6A) modification on oxidized low-density lipoprotein (ox-LDL)-induced mouse monocyte-macrophage leukemic cell (RAW264. 7) pyroptosis. Methods RAW264. 7 cells were treated with 50 μg/ mL ox-LDL for 24 h, and then METTL3 overexpression and knockdown experiments were conducted, and RNA m6A methylation levels were analyzed. Fluorescence quantitative PCR and Western blot were used to measure mRNA and protein expression levels of METTL3, NLRP3, NF-κB p65, GSDMD-N and Caspase-1. Lactate dehydrogenase (LDH) cytotoxicity was used to detect LDH release. Enzyme-linked immunosorbent assays (ELISA) to measure the levels of inflammatory cytokines IL-1β, IL-6, TNF-α, IL-10 and IL-18. Results After ox-LDL stimulation, METTL3 expression and the RNA m6A methylation level were upregulated. Secreted IL-1β, IL-6, IL-18 and TNF-α were significantly increased, while IL-10 expression was decreased after ox-LDL stimulation of RAW264. 7 macrophages (P< 0. 05). On the basis of ox-LDL induction, after METTL3 overexpression, the RNA m6A methylation level was increased, mRNA and protein expression of NLRP3, NF-κB p65, GSDMD-N and Caspase-1 were significantly increased, the levels of proinflammatory cytokines IL-6, TNF-α, IL-1β and IL-18 were increased, the level of anti-inflammatory cytokine IL-10 was decreased, and LDH release was increased. METTL3 knockdown the showed the opposite trends. Conclusions METTL3-mediated m6A modification promotes ox-LDL-induced macrophage pyroptosis and inflammatory responses.