Abstract: To investigate the effects and mechanism of fibroblast growth factor 21(FGF21)on astrocytes in AD-like lesions, Aβ_25-35 was used to induce astrocyte model damaged. Cell model was established by inducing C6 astrocyte cell line and primary astrocyte damage with Aβ_25-35. Different concentrations of FGF21 were used to intervene cell injury model induced by Aβ_25-35, and cell viabilities were detected by MTT assay. Effects of FGF21 and Aβ_25-35 on reactive oxygen species(ROS)levels in C6 cells were tested using DCFH-DA probe and flow cytometry. Western blot was used to assess the effects of FGF21 and Aβ_25-35 on the activities of mitogen-activated protein kinases(MAPKs)in C6 cells. The results showed that FGF21 could reduce the damage of C6 cells and primary astrocytes induced by Aβ_25-35, down-regulate the abnormal ROS level in C6 cells, and alleviate the abnormal phosphorylation levels of MEK1/2, ERK1/2 and p38 in C6 cells induced by Aβ_25-35, suggesting that FGF21 may attenuate Aβ_25-35-induced astrocyte damage by regulating ROS pathway and MAPKs signaling pathway.