[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate whether microtubular structure changes and tau protein hyperphosphorylation exist in hippocampal neurons of experimental diabetic mice, and to study the effect of amyloid precursor protein 17mer peptide. The results showed that the microtubules of hippocampal neurons of diabetic mice manifested prominent signs of fragmentation and dissolution, tau protein is hyperphosphorylated at Ser 199/Thr 202 sites, enzymes related to the phosphorylation and dephosphorylation of tau protein were diminished. The administration of amyloid precursor protein 17mer peptide could ameliorate the foregoing changes in diabetic mice. These results indicated that protein synthesis in the brain tissue of diabetic mice decreased. Amyloid precursor protein 17mer peptide acted as a neuroprotective agent that globally alleviates the disturbances due to impaired energy metabolism in diabetic mice.