Objective To explore the intervention effect and molecular mechanism of engeletin on the proliferation, inflammatory response, and oxidative stress in mouse RAW264.7 macrophages induced by lipopolysaccharide (LPS). Methods RAW264.7 cells were randomly divided into the control group, the LPS group and the intervention groups with different engeletin concentrations. Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay at different culture times. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)and interleukin-1β (IL-1β) in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). The release of cell reactive oxygen species (ROS), superoxide (O₂·^-) and nitric oxide (NO) was detected by corresponding kits. Expression of IκBα, p65 and p-p65 in NF-κB signaling pathway was analyzed by Western blot. Results Compared with the control group, cell proliferation in the LPS group was increased, 100, 200, 400, 600 and 800 μmol/L engeletin could inhibit LPS-induced cell proliferation, and 400 μmol/L engeletin intervention was most effective. TNF-α, IL-6, IL-1β, ROS, O₂·^- and NO produced by cells in the LPS group were higher than those in the control group. 400 μmol/L engeletin could decrease the production of LPS-induced TNF-α, IL-6, IL-1β, ROS, O₂·^- and NO. In the LPS group, protein level of IκBα was down-regulated, and p65 and p-p65 were up-regulated; engeletin could rescue these phenotypes. Conclusion Engeletin may inhibit cell proliferation and the generation of inflammatory factors, ROS/reactive nitrogen species (RNS) in RAW264.7 cells under LPS induction through interfering NF-κB signal pathway. It shows an important anti-inflammatory and antioxidant effect, and provides reference for research of engeletin in the treatment of inflammatory diseases.