Objective To observe the therapeutic effect of acupuncture treatment for chronic fatigue syndrome (CFS). Methods Ninety cases of CFS were randomly divided into an observation group and a control group, 45 cases in each group. The observation group was treated with acupuncture at Renying (人迎 ST 9), Fengfu(风府 GV 16), Batihui (百会 GV 20); the control group was treated with 250 mL 5% Glucose injeetio combined with 20 mL Shenmai injectio (参脉注射液). Fatigue Scale (FS) was used to compare the scores between the two groups after treatment. Results The total scores in the observation group ,were 9.37±2.33 and 5.41±1.96 before and after treatment respectively, and in the control group, they were 9.08±2.27 and 7.34±2.03 respectively. FS brainwork integral, physical fatigue integral, and total integral all decreased after treatment in two groups (all P〈0.001), and it decreased much more obviously in the observation group (P〈0.05, P〈0.01). Conclusion Both of the acupuncture treatment and Shenmai injectio are able to decrease Fatigue Scale score, improve the fatigue symptoms of CFS patients, and the effect of acupuncture treatment is obviously superior to that of Shenmai injectio.