AbstractPurposeThe aim of the study was to investigate the effect of liquiritin on neuroendocrine‐immune network in menopausal rat model.MethodsLiquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E2) and follicle‐stimulating hormone (FSH) in the serum and 5‐hydroxytryptamine (5‐HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin–eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining.ResultsFor the nervous system, liquiritin relieved menopausal depression and up‐regulated the levels of 5‐HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E2 and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen.ConclusionsLiquiritin improved menopausal syndrome in multiple ways by affecting the neuro‐endocrine‐immune network.