Fifty 8-week-old ApoE gene knockout mice were fed with high-fat diet， and after 16 weeks， the ApoE gene knockout mice were randomly divided into model group， low dose of traditional Chinese medicine（TCM） group， high dose of TCM group， acupuncture group， acupuncture+ TCM group；there were 10 rats in each group.Another 10 C57BL/6L mice with the same age fed with normal diet were regarded as control group. From the 17th week， the mice in each group except blank group were given intervention for 8 weeks. After the intervention， the escape latency time of the mice in various groups was observed by Water Maze experiment； the ultrastructures of hippocampus tissue of the mice in various groups were observed by transmission electron microscope； Western blotting and immunohistochemistry methods were used to detect the expression levels of PI3K，AKT and mTOR proteins in hippocampus tissue of the mice in various groups.

The Water Maze results showed that the escape latency time of mice in model group was significantly longer than that in control group （P<0.05）， and the escape latency of the mice in acupuncture group was significantly shorter than that in model group （P<0.05）. The transmission electron microscope observation results showed that the neurons in hippocampal region of the mice in model group appeared deformed， irregular or atrophied， and the nuclear membrane was rough and incomplete， the double-layer structure was fuzzy， and the intracellular phagocytosis was reduced； the neurons in the hippocampal region of the mice in acupuncture group still had some irregular deformation and the arophy and autophagic vesicles could be seen in the cytoplasm. The Western blotting and immunohistochemistry results showed that compared with control group， the expression levels of PI3K， AKT， and mTOR proteins in hippocampus tissue of the mice in model group were significantly increased （P<0.05）； compared with model group， the expression levels of PI3K， AKT， and mTOR proteins in hippocampus tissue of the mice in high dose of TCM group， acupuncture group，and acupuncture+ TCM group were decreased（P<0.05），especially in acupuncture+TCM group （P<0.05）.

The combination of acupuncture and medicine can improve the cognitive function of ApoE gene knockout mice， and its mechanism may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway and promoting the autophagy in hippocampal cells.