Abstract: Objective To study the changes in NGF?NF and PS 1 in the hippocampus of diabetic mice, and to observe the effects of UPAN on the foregoing changes. UPAN is the 63 73 peptide sequence of APP695. Methods Mouse diabetic model was produced with streptozotocin. UPAN was injected subcutaneouly into diabetic mice with dose of 0. 20 ug/per mouse/per day after two weeks . Four weeks later, fixative was injected intravascularly into the mouse. After the brain was fixed, cryostat sections of 40 micrometer thickness were prepared and immunohistochemical staining for NGF?NF and PS 1 were made. Results The use of UPAN could restore protein expression in the NGF?NF and 258 277 peptide sequence of PS 1(141)( P< 0.01). Conclusion UPAN may improve the neurodegenerative changes of diabetic mice.The significance of the increase of the N terminal fragment and the C terminal fragment is to be studied.