Abstract: Objective To study the effect of intragastric botulinum toxin A（BTX-A） on food intake,body weight and expression of ghrelin and NPY in rats and its mechanism underlying anti-obesity. Methods Seventy-two rats were randomly divided into 2-week group,6-week group,and 12-week group（24 in each group）.The 24 rats in each group were further divided into control group,antrum BTX-A group,fundus BTX-A group,and multi-site BTX-A group（6 in each subgroup） to observe their food intake and body weight,plasma ghrelin and NPY levels,immunohistochemical change of ghrelin in stomach and NPY in hypothalamus,and expression of ghrelin-mRNA and NPY-mRNA in stomach and in hypothalamus. Results The food intake and body weight were less in different BTX-A groups than in control group（P＜0.05）.The expression levels of ghrelin and NPY in plasma and gastric tissue were lower in different BTX-A groups than in control group（P＜0.05）.However,they were higher in multi-site BTX-A group than in fundus BTX-A group and antrum BTX-A group（P＜0.05）.The difference gradually became less in the 4 groups 2,6,and 12 weeks after intragastric BTX-A. Conclusion Intragastric BTX-A can decrease the food intake and body weight of rats by down-regulating the expression of brain-gut peptides,such as ghrelin and NPY,which may be one of the mechanisms of BTX-A underlying anti-obesity.