Objective To observe the effect of tetrahydroxy stilbene glucoside (TSG) on the behavior on rat model and the expressions of autophagy-associated protein Beclin-1 and LC3- Ⅱ induced by Aβ1-42 Methods Eighty rats were equally randomized into 4 groups (n =20):The control group,the sham operated group,the model group and the TSG group.The behavior of rats was measured by using Y-maze and Morris water maze.The expression of Beclin-1 and LC3- Ⅱ in rats hippocampus was detected by Western blot and RT-PCR at the time points.Results The number of electric-stimulus in hippocampus significantly increased and the Morris water maze test showed that the escape latency prolonged,swimming distance increased and the times of crossing the exact former platform location decreased both in the model and TSG groups after 21 days compared with those in control group.The mRNAs and protein expressions of Beclin-1 (0.51 ±0.03)and LC3-Ⅱ (0.68 ± 0.04) in model group were higher than that in control group (0.31 ± 0.01,0.31 ± 0.02) at that time point ( Beclin-1:t =28.2843,P ＜ 0.05 ; LC3- Ⅱ :t =37.0000,P ＜0.05).Compared to model group,the expression of the Beclin-1 and LC3- Ⅱ was decreased at 21 d in TSG group (Beclin-1:t =9.8387,P ＜ 0.05 ; LC3- Ⅱ :t =16.2698,P ＜ 0.05 ).Conclusions Autophagy self-regulated system is started through the increased expressions of Beclin-1 and LC3- Ⅱ after Aβ deposition in rats,so as to attenuate cerebral injury caused by Aβ neurotoxicity.Autophagy pathway is possible one of the mechanisms in Aβ neurotoxic injury. Tetrahydroxy stilbene glucoside from polygonum multiflorum has protective effect on it.