AIM: To explore the influence of APP17 peptide on the ultrastructure of hippocampus of the D-galactose induced brain aging model mice. METHODS: APP17-peptide was injected hypodermically into the mice to protect the mice brain aging process. The CA1 area of the mice hippocampus was taken 8 weeks later and observed by electron microscope. RESULTS: (1) There were obvious lysis of the axon microtubule of mice hippocampus, increased swelling mitochondrion with vacuolation. Increased electron density, apparent decrease in the number of ribosomes and rough endoplasmic reticulum, and rarefaction of the synapsis of the neurophil. There was no abnormality in the structure of the hippocampus neurons. (2) In APP17 peptide treated group, the normal microfilament was clearly seen in the microtubule of the mice hippocampus neuron axons; the membrane and the structure of the mitochondrion was normal, the ridges of the mitochondrion could clearly be seen, the rich rough endoplasmic reticulum and ribosomes, the increased synapsis of the neurophils and large amount of clear synaptic vesicles could be seen either. CONCLUSION: D-galactose can cause microstructure abnormalities in the mice hippocampus and APP17 peptide prevent this abnormal structure formation.