Background: In brain insulin does its work through the insulin receptor substrate (IRS). Amyloid beta protein precursor 17 (APP17) peptide has the neurotrophic function, which may improve diabetic encephalopathy resulted from insulin deficiency by affecting insulin receptor substrate. Objective: The mouse diabetic model was produced to observe the effect of APP17 peptide on the distribution of IRS-1 in brain tissues. Design: Randomized control animal experiment. Setting: Staff Room of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences; Beijing Research Laboratory for Brain Aging of Xuanwu Hospital. Materials: The experiment was performed in Staff Room of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory for Brain Aging of Xuanwu Hospital from September to October 2003. Totally 18 male kunming mice were employed, and randomly assigned into control group, diabetic group and APP17 peptide treatment group with 6 mice in each group. Methods: 1 The mice were subjected to intraperitoneal injection of streptozotocin (STZ, Sigma) by 200 mg/kg, and 3 days later, the tail blood was sampled to examine non-fasting blood glucose, and the blood glucose over 15 mmoL/L was set as the criteria for successful diabetic model establishment. 2 In APP17 + diabetes mellitus group, the mice received subcutaneous injection of 0.35 μg APP17 peptide once daily for 2 weeks. The mice in the normal control group were not interfered. 3Then brain was removed and crystat sections were prepared. Immunohistochemical staining was done for IRS-1 at four weeks after giving streptozotocin. Main outcome measures: Pattern and distribution of IRS-1 positive cells of mice in each group. Results: Totally 18 mice were involved in the result analysis. 1In the brains of diabetic mice the IRS-1 immunohistocbemical positive cells distributed at cortex, hippocampus, thalamus, hypothalamus and so on, while the positive cells distributed only at cortex and hippocampus in the normal control group and APP17 peptide treatment group, lightly stained. 2Numhers of immunohistochemical positive cells of IRS-1 of cerebral hippocampus in the diabetic group, normal control group and APP17 peptide treatment group were (28.7±1.5),(9.2±1.5),(10.1±1.4) piece per 10 power object lens, and that in the diabetic group was higher than that in the other two groups (P < 0.001). Conclusion: Neurons in many regions of brains of diabetic mice have plenty of IRS-1 positive cells. APP17 peptide can make part and quantity of IRS-1 positive cells normality so as to ameliorate the degeneration of hippocampal neurons of diabetic mice.