Iron accumulation is considered to be involved in the pathogenesis of Parkinsons disease (PD).The aim of present study is to investigate the mechanism involved in the cytoprotection of Rg1 against ironinduced neurotoxicity in SK-N-SH cells.Significant rescue of Rg1 on cell viability against ferrous iron-induced neurotoxicity was observed.Upregulation of heme oxygenase-1 (HO-1) and Cu-Zn superoxide dismutase (Cu/Zn SOD) were observed in Rg1 pretreated group.Moreover, Rg1 pretreatment induces Nrf2 nuclear translocation,which is upstream of HO-1 expression, and activated PI3K/Akt pathway was also observed in Rg1 pretreated group.This could antaganize iron-induced increase in intracellular reactive oxygen species and decrease in mitochondrial transmembrane potential.These results suggest that the neuroprotective effects of Rg1 against iron toxicity are attributed to the antioxidative properties by activating Akt/Nrf2 pathway and increasing Nrf2-induced expression of HO-1 and Cu/Zn SOD.