Depression has become the most common mental illnesses. Its incidence is increasing yearly and the cause remains unclear. Therefore, it is urgent to explore the pathogenesis of depression and find treatments. In recent years with the continuous increase of research related to depression, intestinal flora have become a new research hotspot in the pathogenesis of depression. Intestinal flora directly and indirectly affect brain functions through various mechanisms and regulate behaviors such as stress, anxiety and depression. This review discusses the relationship between intestinal flora and studies of animal models and clinical depression, the possible regulatory mechanism of intestinal flora in the occurrence and development of depression, and the anti-depressant mechanism of probiotics to provide a new theoretical basis for the treatment of depression by intestinal flora.