Background: Overexpression of phosphorylated Tau protein is a factor of dementia, and scholars abroad find that APP17 peptide may have effect on it. Objective: To observe changes of phosphorylated Tau protein Ser202/ Thr205 of mice with diabetes mellitus (DM) after injection of APP17 peptide. Design: Randomized control study. Setting: Department of Pathology, Capital University of Medical Sciences; Department of Brain Aging, Xuanwu Hospital, Capital University of Medical Sciences. Materials: The experiment was carried out in the Pathological Department of Capital University of Medical Sciences and Brain Aging Department of Beijing Xuanwu Hospital. A total of 18 male Kunming mice of 8 weeks old and weighing 28-32 g were randomly divided into control group, DM group and APP17 peptide group with 6 in each group. Methods: DM models were induced by streptozotocin (STZ) through selectively destroying β-islet cells; meanwhile, APP17 peptide was intraperitoneally injected into mice. Four weeks later, brain tissue underwent immunohistochemical staining with AT-8 (Ser202/Thr205, a special monoclonal antibody). Main outcome measures: 1 Morphological observation; 2 AT-8 distribution; 3 quantitative analysis of immunohistochemical staining. Results: Positive AT-8 cells in DM group were distributed in retrosplenial cortex, hippocampus, thalamus, hypothalamus, etc.; however, those in control and APP17 peptide groups were only distributed in retrosplenial cortex and hippocampus, and poorly stained. Conclusion: Positive AT-8 cells may be widely distributed in neurons of brains of DM mice; however, APP17 peptide may normalize the expression of positive AT-8 cells.