Abstract: It is proposed that the brain Xuanfu and the glymphatic system (GS) have commonality in physiological structure and similarity in functions such as transporting brain substances, transmitting brain information and clearing metabolites. It is believed that GS may be the substantial manifestation of the brain Xuanfu, and GS dysfunction is the key pathological link of depression. Xuanfu stagnation and Shenji dysfunction are the core pathogenesis of depression. Taking "Brain Xuanfu-GS" as the starting point, the pathological mechanism of depression is deeply explored, providing a theoretical basis for the clinical diagnosis and treatment of depression in traditional Chinese medicine.