Abstract：Objective：To observe the effect of Zhisanzhen acupoint on cognitive behavior，the number of γ- aminobutyric acid(GABA)- ergic interneurons and the dendritic spine density in prefrontal cortex and hippocampal CA1 region of model mice with vascular dementia(VD). Methods：A total of 45 male C57BL6J mice were included，and 10 were randomly selected and divided into the sham operation group，and the others were included in the modeling group. The VD models were made by modified repeated clamping method at bilateral common carotid arteries. After successful modeling， the mice in the modeling group were randomly divided into the Zhisanzhen acupoint group， the non- point group and the model group， with 11 mice in each group. Y- maze test and novel object recognition test were used to observe the changes in cognitive behaviors of mice in the four groups. The brain tissue sections were made to observe the changes in the damage situation of pyramidal neurons in hippocampal CA1 region，and the changes in numbers of GABA- ergic interneurons including parvalbumin neurons， neuropeptide Y neurons and somatostatin，as well as dendritic spine density in prefrontal cortex and hippocampal CA1 region in the four groups. Results： Behavioral results showed that the spontaneous alternation rates in the Zhisanzhen acupoint group and the sham operation group were higher than that in the model group，differences being significant(P＜0.05). There was no significant difference being found in the comparison of discrimination ratio toward the same object in mice in different groups(P＞0.05). After 24 hours，the discrimination ratio toward the novel object in the model group was lower than that in the sham operation group and the Zhisanzhen acupoint group(P＜0.05). Nissl staining results showed that the number of pyramidal neurons in hippocampal CA1 region in the Zhisanzhen acupoint group was larger than that in the model group， and some neurons were necrotic and closely arranged. Immunofluorescence results showed that the numbers of parvalbumin neuron， neuropeptide Y neurons and somatostatin in prefrontal cortex and hippocampal CA1 region in the model group were fewer than those in the sham operation group， differences being significant(P＜0.05). The numbers of parvalbumin neuron and neuropeptide Y neurons in prefrontal cortex and hippocampal CA1 region in the Zhisanzhen acupoint group were larger than those in the model group， differences being significant(P＜0.05)，the number of somatostatin in the Zhisanzhen acupoint group was larger than that in the model group，but there being no significance in the difference(P＞0.05). Golgi staining results showed that the dendritic spine density in prefrontal cortex and hippocampal CA1 region in the Zhisanzhen acupoint group and the sham operation group were higher than that in the model group(P＜ 0.05). Conclusion：The application of electro- acupuncture with Zhisanzhen acupoint can protect the pyramidal neurons in hippocampal CA1 region in model mice with VD， and effectively improve the working memory capacity of VD mice.