OBJECTIVE：To investigate the mechanism of sinapic acid （SA）against PC 12 cell injury induced by Amyloid β1-42 protein（Aβ1-42）based on PI 3K/Akt/GSK3β signaling pathway. METHODS：PC12 cells of rats were randomly divided into control group，Aβ group（Aβ1-42 2 μmol/L），Aβ+SA group（Aβ1-42 2 μmol/L+SA100 μmol/L），Aβ+SA+LY group [Aβ1-42 2 μmol/L+SA 100 μmol/L+LY294002（PI3K inhibitor ）10 μmol/L]，Aβ+LY group（Aβ1-42 2 μmol/L+LY294002 10 μmol/L）and LY group （LY294002 10 μmol/L）. Except for control group and LY group ，the cells of other groups were replicated the damage model with Aβ1-42. After 24 hours of culture ，the morphology of cells was obsened in each group with a microscope ，and MTT assay was adopted to determine the cell viability of PC 12 cells in each group. Western blotting assay was used to detect the expression of PI 3K，p-PI3K， Akt，p-Akt，GSK3β and p-GSK3β in cells of each group. RESULTS：Compared with control group ，the number of cells decreased and some synaptic breaks disappeared in Aβ group while cell viability，ratio of p-PI 3K/PI3K，p-Akt/Akt and p-GSK 3β/GSK3β in Aβ group were decreased significantly（P＜0.05 or P＜0.01）. Compared with Aβ group，the cells became round and synapses became more in Aβ+SA group while cell viability，the ratio of p-PI 3K/PI3K，p-Akt/Akt and p-GSK 3β/GSK3β were increased significantly（P＜0.05）. Compared with Aβ+SA group，some synaptic breaks occurred in Aβ+SA+LY group while cell viability， the ratio of p-PI 3K/PI3K，p-Akt/Akt and p-GSK 3β/GSK3β were decreased significantly（P＜0.05）；Aβ+LY group had more cell debris，and t he cell viability was decreased ，but the difference was not significant ，and the ratio of p-PI 3K/PI3K，p-Akt/Akt and p-GSK3 β/GSK3 β had no significant change （P＞0.05）; LY294002 alone had no significant effect on morphology ，cellviability and the ratio of p-PI 3K/PI3K，p-Akt/Akt or p-GSK 3β/ GSK3 β （P＞0.05）. CONCLUSIONS ： SA may play aprotective role against PC 12 cell injury induced by A β 1-42 through activating PI 3K/Akt/GSK-3β.