Abstract: OBJECTIVE To study the effect and mechanism of antrodia camphorata polysaccharide (APC) resistance to the inflammatory reaction of PC12 cell which was induced by lipopolysaccharide (LPS). METHODS After routine culture, PC12 cell was divided into control group, model group, high and low dose of APC group. The low dose group was treated with 10 mg·L^-1 APC. The high dose group was treated with 50 mg·L^-1 APC. Cell viability was detected by CCK-8. Observated the cell morphology under light microscope, calcium intracellular ions detected by Fluo 3-AM fluorescence probe on Laser confocal microscope. The expression of TLR4, MD2 and downstream MyD88 were dected by Western blot. The expression of TNF-α, IL-6 and IL-1β dected by ELISA. The mRNA expression of MD2, TLR4 and MyD88 dected by RT-QPCR. RESULTS APC could significantly reduce the neuro inflammation induced by LPS. The cell survival rate in APC group was significantly higher than that in the model group, and the high dose group was better than the low dose group. After APC intervented, the expressions of MD2, TLR4 and downstream MyD88 were significantly down regulated, the expressions of TNF-α, IL-6 and IL-1β were also down regulated, the high dose group was superior to the low dose group. CONCLUSION APC can resist the neuroinflammation induced by LPS. The mechanism is related to inhibiting the TLR4-MD2 and its downstream factors. It provides a new reference for the treatment of nerve diseases and application of APC.