To study the effect of electric acupuncture on the transforming growth factor (TGF)-β1 signaling pathways of the chronic fatigue syndrome (CFS) rat model. Methods: Forty-eight SD rats were randomly assigned to the normal group, model group, bound group, and acupuncture group with 12 rats per group. The CFS rat model was established by applying multiple chronic stress factors. The bound group rats were subject to binding for an equal duration of time as that of the acupuncture treatment applied to the acupuncture group rats. Acupuncture group rats were treated for 15 days by electric acupuncture to the Baihui acupoint, frontal lobe area, and parietal lobe area. TGF-β 1 mRNA transcription was tested by RT-PCR, and TGF-β 1 expression was assessed by Western blot. Results: Model group and bound group rats showed significantly increased TGF-β1 mRNA transcription levels in the hippocampus and hypothalamus compared to normal group rats (P<0.01); there was no significant difference between the acupuncture group and normal group (P>0.05). The acupuncture group showed significantly decreased TGF-β 1 mRNA transcription levels compared to the model group (P<0.01) while the bound group and model group showed no significant difference (P>0.05). The normal group displayed lower TGF-β1 expression compared to the other 3 groups (P<0.01). Acupuncture group rats showed significantly decreased TGF-β1 expression levels in the hippocampus and hypothalamus compared to model group rats (P<0.01); the bound group and model group showed no significant difference (P>0.05). Conclusion: Electric acupuncture can reduce TGF-β1 mRNA transcription levels and TGF-β1 protein expression in the hippocampus and hypothalamus of CFS model rats