Objective To investigate the effects of analog 165 of APP5-mer peptide on the expression of synaptic related proteins in neurons of the hippocampus through intracerebroventricular(ICV) injection of streptozotocin(STZ) in rats. Methods A total of 45 Wistar rats were randomly divided into control group, model group and treated group. Rats in the model and treated groups received intracerebroventricular injection of STZ bilaterally. After three weeks, rats in the treated group received gastric perfusion of analog 165 of APP5-mer peptide. After the fourweek treatment, the memory of the rats was surveyed by Morris water maze test.The expressions of synaptic related proteins, such as postsynaptic density_95 protein(PSD-95), synaptophysin and α-Synuclein, were tested with immunohistochemical staining and Western blotting. The ultrastructure of the neurons of hippocampus was observed with transmission electron microscope. Results 1.Fullcourse swimming time was obviously longer in the model group than that those in the treated and control groups. 2.In the model group, the expressions of PSD-95 and synaptophysin decreased,and the expression of α-Synuclein increased. The treated group normalized the expression of the targeted proteins. 3.Retrograde degeneration of the neurons of hippocampus was observed in the model group, and dysmorphic synapses were observed in the neuropil. Conclusion There are low PSD-95, synaptophysin levels and high α-Synuclein levels in the ICV injected brain of STZ rats. Analog 165 of APP5-mer peptide improves the expression of the three proteins to some extent; therefo