Abstract: Objective To investigate the phosphorylation levels of tau in hippocampus of type 1 and type 2 diabetic rats, and its possible mechanism. Methods The models of type 1 (T1DM) and type 2 diabetes (T2DM) were made，and controlled by the same age rats(CTL). The plasma insulin and the plasma glucose levels were determinated by RIA and glucose-oxidase methods, respectivly.The indexes of insulin resistance were calculated by HOMA-IR. Total tau protein and phosphorylation levels (pSer199,pThr212, pSer214, pSer396 and pSer422) of tau were analyzed by Western blot. The activity of glycogen synthase kinase -3β(GSK-3β), a key component of insulin signal transduction pathway and a known tau kinase, in hippocampus of rats was examined by γ32P-ATP and its specific substrate. Results Plasma glucose was significantly higher in T1DM and T2DM group than in CTL group, and the plasma insulin was significantly higher in T2DM group but lower in T1DM group than in CTL group. Insulin resistance, which was calculated by HOMA-IR, was significantly higher in T2DM than in T1DM and CTL group. Tau protein is hyperphosphorylated at several Alzheimer disease(AD)-related phosphorylation sites (Ser199,Thr212 and Ser396). The activity of GSK-3β also increased significantly in the brains of both diabetic models. Conclusions These findings suggest that type 1 and type 2 diabetes increase the probality of AD by downregulation of insulin signal transduction and the consequent upregulation of GSK-3β, which leads to hyperphosphorylation of tau protein.