Abstract: The incidence rate of depression is increasing, but its pathological mechanism is still unknown. More evidence shows that the occurrence and development of depression is closely related to the changes of gut microbiome. However, due to the huge differences in bacterial composition among individuals caused by different environmental factors, researchers usually need a large number of samples to get reliable results. Experimental animal models play an important role in the pathogenesis of diseases and the mechanism of drug action because of their highly consistent background, controllable experimental environment, and the characteristics of artificial intervention. Therefore, the selection of appropriate experimental animal models can not only simulate the clinical symptoms of human depression, but also reveal the causal relationship between clinical characteristics and gut microbiome changes. In this review, the development and application of fecal microbiota transplantation technology, the close relationship between flora and depression, the application of humanized fecal microbiota transplantation experimental animal model in the study of depression, as well as the preparation methods and key technologies of humanized fecal microbiota were summarized, which provided a reference for the research on the pathogenesis of depression and the mechanism of antidepressant drugs of humanized fecal microbiota transplantation experimental animal model. This review provides a reference for the reasonable application of this aspect.