Objective To observe the effects of electro-acupuncture (EA) on body weight, insulin resistance, hypothalamic agouti gene-related protein (AGRP) and neuropeptide Y (NPY) in diet induced obesity (DIO) rats; To discuss its mechanism for DIO.Methods Fifty SD male rats were randomly divided into low fat diet groups (LFD) and high fat diet group. After the DIO models were established, the successful model rats were randomly divided into model group, EA group and Orlistat (OLST) group. EA was applied to “Zusanli” (ST36) and “Quchi” (LI11) for 20 minutes. The treatment was done once a day for 28 days. OLST was treated with orlistat by gavage. LFD and model did not receive treatment. Body weight was recorded every day. FPG and FINS were detected. The expressions of AGRP and NPY were detected by RT-QPCR. Morphological changes of adipocyte and liver were examined by HE staining.Results The body weight, HOMA-IR, AGRP, NPY and diameter of adipocyte of EA group and OLST group were significantly lower than model group (P<0.05), difference between EA group and OLST group. The states of hepatic steatosis were improved in EA group and OLST group.Conclusion EA has the effects on weight loss by inhibiting the expressions of AGRP and NPY by improving IR.