AbstractBisphenol A‐glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three‐dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti‐inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti‐inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 μM for 30 min before being incubated with BisGMA at 0 or 3 μM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme‐linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA‐induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and PGE2, in macrophages. Rutin also suppressed the BisGMA‐induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration‐dependent manner. Furthermore, rutin suppressed the mitogen‐activated protein kinase (MAPK) phosphorylation in a concentration‐dependent manner. Finally, rutin suppressed the BisGMA‐induced phosphorylation of nuclear factor (NF)‐κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF‐κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti‐inflammatory agent for BisGMA‐stimulated macrophages through NF‐κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.