Objectives: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS., Methods: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups ( n =9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) β1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-β1 in hippocampal CA1 region were detected by immunofluorescence staining., Results: Compared with the control group, the score of general condition was increased ( P <0.05), the escape latency was prolonged ( P <0.05), the number of crossing the original platform was decreased ( P <0.05), the numbers of crossing the grid and entering the central area were increased ( P <0.05), and the exhaustive treadmill time was shortened ( P <0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased ( P <0.05), while IL-17 and TGF-β1 contents were increased ( P <0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased ( P <0.05), while the intensity of IL-17 and TGF-β1 were increased ( P <0.05). After treatment, compared with the model group, the score of general condition was decreased ( P <0.05), the escape latency was shortened ( P <0.05), the number of crossing the original platform was increased ( P <0.05), the numbers of crossing the grid and entering the central area were decreased ( P <0.05), and the exhaustive treadmill time was prolonged ( P <0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased ( P <0.05), while IL-17 and TGF-β1 levels were decreased ( P <0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased ( P <0.05), while the intensity of IL-17 and TGF-β1 were decreased ( P <0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group., Conclusions: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.