Abstract： It was hypothesized that the VPAC1 agonist may exert anti-obesity functions because VPACI is involved in the anorexigenic effects and the anti-inflammatory function of pituitary adenylate cyclase-activating polypeptide(PACAP)/vasoactive intestinal polypeptide(VIP).Furthermore,our in vitro test showed that the expression of VPAC 1 increased significantly after the 3T3-L1 adipocytes were differentiated,and that incubation of adipocytes with VPACI agonist(10-1 000 nmol/L per 1x 106 cells)resulted in stimulation of lipolysis.To test the effect of VPAC1 agonist[Lys15,Arg16,Leu27]-VIP(1-7)GRF(8-27)on diet-induced obesity(DIO),we fuaher designed the following two in vivo experiments:(1)Mice were fed on high-fat diet(HFD)and intraperitoneally(i.P.)treated with VPAC 1 agonist simultaneously for 28 d;(2)Mice were given HFD for 35 d,and subsequently fed on the same HFD and i.p.treated with VPAC1 agonist for the next 28 d.The physiological indices,including body weight,weight of white adipose tissue,plasma glucose and b100d lipid.were collected.The results showed that treatment with VPAC1 agonist inhibited ingestion significantly and prevented the elevations in bedv weight and the weights of the white adipose tissues(epididymai and dorsal)induced by HFD.The increases in plasma glucose,cholesterol,triglycerides and LDL induced by HFD were also down-regulated in mice treated with VPAC1 agonist.VPAC I agonist treatment also improved the glucose tolerance.Therefore,VPAC1 agonist treatment inhibits the development of the obesity induced by HFD and helps to improve the morbidities associated with DIO.