Objective To investigate the effects of intracerebroventricular（ICV） administration of streptozotocin (STZ) on expression of PSD-95 and Shank1 in rat hippocampus. Methods A total of 30 rats were randomly divided into normal control group and model group. The rats in the model group received intracerebroventricular injection of STZ bilaterally with a dose of 3mg/kg and the injection was repeated on the third day. The rats in normal control group received the same treatment as the first group except for STZ injection. After 21 days, the brains of the rats were taken, frozen sections of brain were prepared, and then PSD-95 and Shank1 were stained with immunohistochemistry. Furthermore, the contents of PSD-95 and Shank1 were detected by Western blotting. Results After ICV injection of STZ, the expression of PSD-95 and Shank1 positive cells and the contents of PSD-95 and Shank1 in hippocampus both decreased. Conclusion ICV injection of STZ can lead to the decrease of the expression of PSD-95 and Shank1, indicating it may damage the neuron’s synaptic signal