Depression is a chronic syndrome with a complex etiology, and heterogeneity of clinical manifestations in depressed patients suggests diversity in pathogenesis. In order to improve the quality of life of patients with different depression, it is urgent to explore the representative pathogenesis. Studies have found that peripheral circulating hormones can through the blood-brain barrier into the brain, and brain hippocampus tissue can also cholesterol as raw material independent synthesis sex hormone, into the brain peripheral circulating hormones and the brain synthesis of brain hormones together micro environment, the sex hormone of sex hormone microenvironment disorder is one of the important mechanisms of depression. Traditional Chinese medicine can improve the homeostasis of sex hormones and regulate the downstream signaling pathway by affecting the level of peripheral hormone, or regulating the key enzymes in the synthesis or decomposition of the brain signaling. However, the synthesis and catabolic capacity of incretion in the brain and the main pathways and key role targets in antidepressant TCM are unclear. Based on the “sex hormone-receptor-key enzyme” trinity of the sex hormone microenvironment homeostasis regulation is interpreted with multiple ways, targets, integrity characteristics of the combination of antidepressant mechanism of innovative research ideas, this paper will be the traditional Chinese medicine through regulating sex hormone microenvironment homeostasis treatment of depression research progress.