Objective: To investigate the effects of electro-acupuncture on obestatin in rat with simple obesity. Methods: Obesity was induced in male SD rats with high-fat and -glucose diet for 10 weeks. Twenty-four rats with obesity were randomly divided into untreated group and electro-acupuncture group, with 12 rats in each group. Another 12 normal SD rats serving as controls were fed standard rat chow. Rats in the electro-acupuncture group were treated with electro-acupuncture on bilateral Zusanli (ST36), Tianshu (ST25) and Pishu (BL20) acupoints for fifteen days consecutively. Rats in the blank control group and untreated group were not interfered. Body weight was measured every 3 days during treatment. After treatment, obestatin in serum and hypothalamus was detected by radioimmunoassay or immunohistochemiscal method respectively. Visceral fat weight was also detected. Results: Body weight and visceral fat weight of rats in the untreated group were significantly higher than those in the blank control group (P<0.01). Body weight and increase of body weight in the electro-acupuncture group were significantly lower than those in the untreated group (P<0.01). Visceral fat weight in the electro-acupuncture group was significantly lower than that in the untreated group (P<0.01), but there was no significant difference as compared with the blank control group. The obestatin expression in hypothalamus was higher in the untreated group than in the blank control group (P<0.05), while it was lower in the untreated group than in the electro-acupuncture group (P<0.01). Conclusion: Electro-acupuncture has an effect against obesity in rats, which may be related to up-regulating obestatin expression in hypothalamus.