Objective: To observe the effect of curcumin on the expression of PI3K (phosphatidylinositol-3-kinase, PI3K) and p-PI3K (phosphated phosphatidylinositol-3-kinase, p-PI3K) in the hippocampus of Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice. Method: A total of 60 three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group (10 mg·kg-1·d-1) and curcumin large(400 mg·kg-1·d-1), medium(200 mg·kg-1·d-1) and small(100 mg·kg-1·d-1) dose group. Twelve C57BL/6J mice in the same age and genetic background as APP/PS1 double transgenic mice were used as normal control group. All the 6 groups of mice were intragastrically administered for 3 months. After 3 months, the expression of PI3K and p-PI3K were detected by immunohistochemistry and Western blot. Result: The expression of PI3K and p-PI3K positive cells in hippocampus CA1 region significantly decreased in model group compared with normal control group (P<0.05), while compared with model group, PI3K and p-PI3K positive cells of all the curcumin intervention groups increased to varying degrees in hippocampus CA1 region, especially the middle dose group(P<0.01). Besides, Western blot results of the curcumin high dose group were also increased obviously (P<0.05). Conclusion: Curcumin can recover the decreased PI3K and p-PI3K and improve the insulin-signaling transmission in the hippocampus of APP/PS1 double transgenic mice. The mechanism of curcumin maybe by regulating the insulin signal transduction to treat AD.