Objective: In this report, the effects of cynomorium flavonoids on mouse model of perimenopausal depression were investigated. Method: 60 ovariectomized female mice were randomly divided into 6 groups evenly: high, medium and low doses of cynomorium flavonoids groups (400mg·kg-1, 200mg·kg-1, 100mg·kg-1), Gengnianan capsule group (675mg·kg-1), soy isoflavones soft capsule group (250mg·kg-1), and model group. Give the corresponding drug fifth days after surgery for once a day, consecutive thirty days. The model group and control group given the water of same volume. The model related groups were applied with different stress for consecutive eighteen days. Kill the mice and remove the thymus, spleen, uterus and one hand of brain when it is 2 hours after the last administration in mice of each group. Observe the histological changes of each group under light microscope. Results: By observing the pathological section. Compared with modelgroup, the pathological changes of the uterus and hypothalamus of mice were significantly improved. The thymic cortex markedly thickened, volume of splenic nodule also significantly increases, the number of lymphocytes significantly increased (P < 0.01). Simulation results that the high dose of cynomorium flavonoids group has the best effective. Conclusion: Cynomorium flavonoids on mouse uterus, hypothalamus, thymus and spleen lesions have a significant role in the improvement. Cynomorium flavonoids have a good therapeutic effect on mice with perimenopausal depression