Aim: To investigate the effect of APP17 peptide on apoptosis of hippocampus neurons in mice with D-galactose induced brain aging and to provide theoretical basis for the clinical treatment for brain aging by APP17 peptide. Methods: Sixty six male Kunming mice were randomly divided into 3 groups: control group (C group). D-gal control group (D group), APP17 peptide treatment group (P group) with 22 mice in each group. D-gal mouse models were established by injection of D-gal and treated by subcutaneous injection of APP17 peptide. The immunohistochemical stainning of brain tissue sections were then performed with B-cell leukaemia/lymphoma-2 (Bcl-2), Bax, cAMP response element binding protein (CREB), Ser-Thr kinase B (Akt), apoptosis inducing factor (AIF) antibody after 3 months. Results: Number of Bax, AIF positive neurons were widely increased in the hippocampus of the D-gal miceadn there was a significant difference in cell counting when compared with C group and P group; Cytoplasm and processes were darkly stained. In healthy and APP17 peptide-protected D-gal mice. Bcl-2. CREB, Akt positive cells increased and cytoplasm were deeply stained, significant difference in cell counting when compared with D group. Conclusion: The expressions of Bax and AIF (apoptosis inducing factors) can be increased in the hippocampus of D-gal mice. While the expressions of Bcl-2, CREG and Akt decreased in hippocampus of D-gal mice. The APP17 peptide can make them normal.