To investigate the effects of electroacupuncture on the learning and memory capabilities and serum levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interferon-γ (IFN-γ) in rats with chronic fatigue syndrome. Methods: Thirty-six male SD rats were randomly divided into the control group, model group, and electroacupuncture group, with 12 rats in each group. The electroacupuncture group and model group were subjected to forced weight-bearing swimming and chronic stress stimulation for 28 days. The electroacupuncture group was treated with electroacupuncture from the 14th day after modeling. The bilateral sensory area, Baihui point, and Ningshen point were selected for electroacupuncture, and continuous treatment was given for 14 days. The model group was bound for the same length of time but was not treated. After treatment, the learning and memory capabilities of rats were evaluated by the Morris Water Maze test. Blood was drawn and centrifuged to isolate serum, and changes in serum TNF-α, IL-10, and IFN-γ were detected by ELISA. Results: In the Morris water maze test, compared with that of the control group, the escape latency in the model group was prolonged (P<0.01) and the number of platform crossings was decreased (P<0.01). Compared with the model group, the escape latency in the electroacupuncture group was shortened (P<0.01) and the number of platform crossings increased (P<0.01). In addition, the serum levels of TNF-α and IL-10 were significantly increased and that of IFN-γ significantly decreased in the model group compared to those in the control group (all P<0.01). The serum levels of TNF-α and IL-10 were significantly decreased and that of IFN-γ significantly increased in the electroacupuncture group compared to those in the model group (all P<0.01). Conclusion: Electroacupuncture can significantly improve the learning and memory capability and regulate the serum inflammatory cytokine levels of rats with chronic fatigue syndrome .