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Objective: Study the effect of electroacupuncture on permenopausal depressive disorder (PDD) model through the peri-menopausal depression model mice. Methods: KM female mice were selected. Except for the blank group (BG), the other groups of mice were removed by castration method. The mice of PDD was prepared by combining chronic unpredictable stimulation. Mice in the model group (MG) were not treated and fed normally. The western medicine group (WG) was given the corresponding drug for treatment. The electroacupuncture group (EAG) was given the electroacupuncture for treatment, and consecutive for 28 days. The levels of T, E2, FSH and LH in serum of mice were measured, and the brain tissue of 5-HT, DA and NE level were measured. Through the HE staining observed the morphological changes of mice hypothalamus. Results: Compared with MG, EAG could increase the number of spontaneous activities of PDD model mice, the level of T, E2 in serum and the level of 5-HT, DA, NE in brain tissue was improved, and the level of FSH, LH in serum was reduced, and the hypothalamic lesions was improved. Conclusion: Electroacupuncture could improve the activity and memory of PDD mice, adjust the disorder of sex hormone, and increased the levels of monoamine transmitters (5-HT, NE, DA), and it could effectively improve the behavior and related biochemical indexes of PDD, and thus play an important therapeutic role. Keywords: PDD, Electroacupuncture, Behavior indexes, Biochemical indexes, Histopathologic morphology