Objective: To investigate the mechanism of electroacupuncturein treating chronic fatigue syndrome(CFS) in term of the neuro-endocrine system by observing the regulative effect of EA on hypothalamic-pituitary-adrenal index (HPA index) and corticotropin releasing hormone mRNA (CRH mRNA) in CFS model rats. Methods: The rats were randomly divided into control group, model group, and electroacupuncture group. Model and electroacupuncture groups were forced to swim in cold water to make CFS model, while rats in electroacupuncture group were treated with electroacupuncture treatment at the same time. Electroacupuncture group was given at Baihui(GV 20) and Zusanli(ST 36). Evaluation of the model was processed according to the behavior changes of the rats. Hypothalamic, pituitary, and adrenal were weighted to calculate HPA index. CRH mRNA in hypothalamic was measured by fluorescence quantitative polymerase chain reaction (FQPCR). Results: The model rats had behavior changes, and both physical and mental fatigue was observed. HPA index raised and expression of CRH mRNA in hypothalamus increased in CFS rats. After electroacupuncture treatment, the physical and mental fatigue was improved, and the hypothalamic index and CRH mRNA decreased significantly, while the pituitary and adrenal index only had little decrease. Conclusion: Cold water swim press could mimic the pathogenesis and make similar manifestations in rats with the common clinical symptoms. CFS has close relationship with increase of HPA index and CRH mRNA expression. Electroacupuncture can regulate the function of HPA axis to deal with CFS.