Objective To investigate the effect of insulin signaling pathway on neuronal survival and the effect of the peptide App17 on regulating the expression of some apoptosisrelated proteins in neurons of the hippocampus through intracerebrorentricular injection of streptozotocin in rats. Methods The rats were injected with App17 peptide subcutaneously three weeks after the model group was established by intracerebrorentricular injection of streptozotocin. After the fourweek treament, the expressions of the apoptosisrelated proteins, such as Bcl-2, Bax, CytoC in neurons of the hippocampus were tested with immunohistochemical staining and Western blotting. Results Bax, CytoC positive neurons were widely distributed in the hippocampus of the model group, and the cytoplasm was darkly stained. In contrast, the positive neurons for Bax, CytoC in hippocampus were poorly stained in the control group and the treated group, and appeared significant difference in cell counting as compared with model group. Bcl-2 positive neurons were widely distributed in the hippocampus in the control group and the treated group, and the cytoplasm was darkly stained while its positive neurons were poorly stained in the model group, and appeared significant difference in cell counting as compared with the model group. From the Western blotting clear bars could be seen in the three groups and there was a significant difference between them.Conclusions The expression of Bax, CytoC increased in the hippocampus in the rats with intracerebrorentricular injection of streptozotocin while the expression of Bcl-2 decreased. The App17 peptide could promote the rehabilitation of the abnormal expression of the three proteins to some extent. The insulin signaling pathway could affect the survival of the neu