Abstract：To investigate the preventive effect of ginsenoside on the spatial reference memory impairment in Senescence Accelerated Mouse Prone 8 (SAMP8) and the mechanisms, in the present study, SAMP8 mice aged 4 months were chronically treated with ginsenoside (given in drinking water: in 3 dose groups and for 7 months). The 3 dose groups were administered with ginsenoside of 50, 100 and 200 mg/kg per day, respectively. Placebo-treated aged mice and young mice(4 months old) were used as controls. In addition, Senescence Accelerated Mouse Resistant 1 (SAMR1) mice were used as "normal aging" control. The beneficial role of ginsenoside was manifested in the prevention of spatial reference memory loss in aged SAMP8 mice. The optimal dose of ginsenoside is 100 or 200 mg/kg per day. In ginsenoside treated groups, the antioxidase level in serum is significantly increased. However, the neurons damage level of the ultrastructure and the Aβ1-42 level markedly decreased in hippocampus. These findings suggest that the increase of antioxidation may be one of mechanisms of the memory loss prevention of ginsenoside in aged SAMP8 mice.