Objective To investigate the anti-inflammatory and antioxidant effects of liensinine ( LIE) derived from lotus on a lipopolysaccharide (LPS)-induced RAW264. 7 macrophage inflammatory model, and to study the molecular mechanisms responsible for these effects in relation to the nuclear factor ( NF-κB), mitogen-activated protein kinase (MAPK), and nuclear factor-erythroid factor 2-related factor 2 ( Nrf2) / heme oxygenase ( HO)-1 pathways. Methods RAW264. 7 macrophages were divided into Control group, LPS group and LIE ( 0. 5, 1, 2 μmol / L) groups. Cells were subjected to Cell Counting Kit 8 screening of non-cytotoxic concentrations of LIE, nitric oxide (NO) was detected by the Griess method, prostaglandin 2 (PGE2) and pro-inflammatory factors (TNF-α,IL-6 and IL-1β) were detected by enzyme- linked immunoassay, cyclooxygenase-2 ( COX-2) and inducible nitric oxide ( iNOS ) synthase gene expression were detected by real-time polymerase chain reaction, and reactive oxygen species (ROS) were detected by dichloro-dihydro- fluorescein diacetate assay ( which detects superoxide dismutase ( SOD ) activity and glutathione ( GSH ) and malondialdehyde (MDA) contents), and NF-κB, MAPK, and Nrf2 / HO-1 pathway protein expression were detected by Western Blot. Results LIE 0 ~ 4 μmol / L had no effect on cell viability. Levels of pro-inflammatory factors levels were significantly lower in the LIE (0. 5, 1, 2 μmol / L) group compared with the LPS group, NO and PGE2 concentrations and COX-2 and iNOS mRNA expression levels were all decreased, and NF-κB and MAPK pathways were inhibited ( P< 0.05) in dose-dependent manners. The ROS and MDA contents were also significantly lower and SOD activity and GSH were significantly higher compared with the LPS group (P< 0.01), and the activity of the Nrf2 / HO-1 pathway was also significantly higher than that of the LPS group (P< 0.05). Conclusions LIE exerts anti-inflammatory and antioxidant effects by inhibiting the NF-κB and MAPK pathways and activating the Nrf2 / HO-1 pathway.