The aim of the present study was to investigate the anti-inflammatory effects of astragalin (Ast) isolated from Aster scaber in lipopolyssacharide (LPS)-stimulated Raw264.7 macrophage cells, and the neuroprotective effect of Ast against nitric oxide-induced neuronal cell death. The ethyl acetate fraction of Aster scaber had the highest 2,2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity among the ethanol extracts and the five fractions. Cells were pretreated with Ast isolated from the ethyl acetate fraction of Aster scaber and further cultured for an appropriate time after LPS addition. Ast reduced the concentration of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the Raw264.7 cells activated by the LPS. These inhibitory effects were attributed to the suppression of the mitogen-activated protein kinase (MAPK) pathways by Ast. Sodium nitroprusside (SNP) was used as the NO donor. Ast increased the survival of human SK-N-SH neuroblastoma cells exposed to toxic conditions due to the excessive production of NO. The effect of Ast was observed in co-cultured cells (SK-N-SH cells and microglia). Treatment of SK-N-SH cells with Ast showed protective effects against SNP-induced NO production in microglia. These results suggest that Ast could act as a potential neuroprotective agent via its anti-inflammatory effects.