Abstract: OBJECTIVE To observe the effect of electro-acupuncture on central conditional knockout Stat5 Nestin-Cre obese mice (Stat5NKO) and detect how the obesity related genes， Kctd15 and Sh2b1， are involved. METHODS 20 obese Stat5NKO mice were randomly divided into two groups: obese model group (n=10) and electro-acupuncture （EA） group (n=10); 10 Stat5fl/fl mice were randomly selected and fed with ordinary forage as normal control group. EA group was treated with electro-acupuncture at Housanli and Neiting points for 30 min， with bilateral alternates， by Han' electro-acupuncture apparatus at 2/15 Hz. 6 d was a period of treatment， with a total of 4 courses of treatment. Serum Leptin content was measured by ELISA， and the levels of Sh2b1 and Kctd15 mRNA in hypothalamus were detected by qPCR. RESULTS Compared with Stat5fl/fl mice， Stat5NKO mice gained body weight significantly (P<0.01)， accompanied with increased serum Leptin level (P<0.05)， decreased hypothalamic Leptin level (P<0.05)， as well as Kctd15 and Sh2b1 mRNA expressions (P<0.05~0.01); Compared with Stat5NKO mice， EA group decreased body weight (P<0.01) and serum Leptin mRNA level (P<0.01). The hypothalamic Leptin level was elevated (P<0.01)， and the expressions of Kctd15 and Sh2b1 mRNA were returned to normal level (P<0.01). CONCLUSION The weight-loss effect of electro-acupuncture on Stat5NKO obese mice may be related to the regulation of the expression of Leptin， Kctd15 and Sh2b1.