To established β-amyloid peptide (1-40) (Aβ SUB>1-40/SUB>) and D-galactose(D-gal) AD rat models and to explore the anti-oxidation molecular mechanism of the Gastrodin and provide the experimental foundations for clinical treatment of AD. AD rat models were established by lateral ventricle injection of Aβ1-40 and abdominal cavity injection of D-gal (100 mg/kg) to thirty six male SD rats. Meantime, the rats were treated by intragastric administration the Gastrodin. Then the behavioral testing of experimental rats was performed by the Morris water maze(MWM). The thiol antioxidants including hydrogen peroxide (HSUB>2/SUB>O SUB>2/SUB>), glutathione reductase (GR) and glutathion (GSH) activities were examined by colorimetric method. The concentration of the p38 and P-p38 was examined respectively by Western blotting. The AD model rats when compared with control group exhibited a significant increase in escape latencies (EM> P/EM> <0.05), and a decrease in the time of staying at the third quadrants of platform and the degree of crossing over a platform. The cerebral cortex concentration of the H2O2 was increased, and the concentrations of the GR and GSH were decreased ( EM>P /EM><0.05). The expression of P-p38 was increased (EM> P/EM> <0.05). After the treatment with Gastrodin, the AD model rats exhibited a significant decrease in escape latencies ( EM>P /EM><0.05), an obvious increase in the time of staying the third quadrants of platform ( EM>P/EM> <0.05) and the increase of crossing over a platform (EM> P/EM> <0.05) when compared with the AD group ( EM>P /EM><0.05). The concentration of the H2O2 was decreased, the concentrations of GR and GSH were increased ( SUP>P /SUP><0.05). The expression of the P-p38 was less than that of the AD model ( EM>P /EM><0.05). But there were no significant differences between the three groups in the expression of the p38 ( EM>P/EM> >0.05). Gastrodin could improve the oriented learning and memory capacity and prevent the neurodegeneration of central nervous systems in AD model rats by partly affecting the expression of the thiol antioxidants(e.g. GR and GSH) and the expression o