Abstract: Objective To investigate the effect of APP 17 mer Peptide on some proteins related to insulin and apoptotic signal transduction pathways in the hippocampus of diabetic rat brain.Methods The diabetic rat model was produced by intraperitoneal injection of streptozotocin and some of the diabetic rats were treated by APP 17 mer peptide. Immunoprecipitation and Western blot were used to analyse the proteins related to the insulin and apoptosis signal transduction pathway. Electron microscope was used to examine the ultrastructural change of the hippocampal neurons.Results In the hippocampus of the diabetic brain, IGF IRα, Akt/PKB and CREB involved in the insulin transduction pathway were decreased, while GSK 3β, PP 1, Bax and AIF related to apoptosis signal transduction pathway were increased. In addition, the hippocampal neurons of the DM rat showed degenerative changes. APP 17 mer peptide partially corrected the changes of the above protein and improved the degenerative changes of the hippocampal neurons. Conclusion Some of the important proteins are abnormally expressed in the insulin and apoptosis signal transduction pathways in the hippocampus of diabetic rat brain. APP 17 mer peptide can partially correct the abnormal expression, which may be related to its protective effect on hippocampal neurons of the DM rat.