Objective：This study was designed to explore the brain insulin signaling and the expression of glucose transporters（GLUTs）in APP/SP1 transgenic Alzheimer’s disease（AD）mice，it may provide the evidence for the early diagnosis of AD. Methods：Western blot was used to detect the expressions of insulin-signaling pathway related proteins in the cortex and hippocampus of the APP/PS1 transgenic AD model mice. Results：Our results showed that in the 3-month-old mice，brain insulin signaling was irritably activated，and the phosphorylation level of downstream AKT/GSK3β and other insulin signaling molecules increased，while the expression of GLUTs did not change significantly at this time. However，in the 5-month-old mice，it showed that the phosphorylation level of the brain insulin signal decreased significantly，and the phosphorylation level of its downstream AKT/GSK3β and other signaling molecules was down-regulated. At the same time，down-regulated expression of GLUT3 and GLUT4 was observed in the hippocampus，and the level of Tau protein phosphorylation（p-tau）was significantly increased. Conclusion：Our results confirmed that in APP/PS1 transgenic mice，brain insulin signaling pathway and glucose homeostasis were significantly disrupted in the process of AD formation，and the impairments increase with age.