Chronic fatigue syndrome(CFS) is a neuroimmune disease characterized by unexplained fatigue for a long time and inability to recover energy after sleep.As a key factor regulating the central nervous system，intestinal flora participates in the occurrence and development of CFS.To clarify the mechanism of intestinal flora in the pathogenesis of CFS，this paper analyzed the intestinal flora and its metabolites affecting CFS based on the microorganism-gut-brain axis，and discussed the internal mechanism of intestinal flora imbalance in weakening endotoxin tolerance，destroying intestinal barrier，changing intestinal flora metabolism to regulate the central nervous system of CFS.The paper facilitates the further research on intestinal microorganisms of CFS patients and provide a new clinical idea for the prevention and treatment of CFS.