Objective:To investigate the role of orexigenic and anorectic neuropeptides in hypothalamic arcuate nucleus in chronic energy restricted mice. Methods:Twenty－four C57BL/6J male mice were randomly divided into high fat diet group and normal diet group. After 8 weeks,6 mice of each group were given energy restricted diet (85% of normal or high fat diet). The mice were sacrificed after another 6 weeks. The body weight was determined every week during the 14 weeks feeding study. The neuropeptides mRNA expression levels from hypothalamic tissue were analyzed after sacrifice. Results:The energy restricted diet reversed obesity,and increased NPY and AgRP mRNA expression of hypothalamic arcuate nucleus after 6 weeks(P < 0.001). POMC and CART mRNA expression were not changed significantly. Conclusion:Chronic energy restriction leads to weight loss,but it also up－regulates hypothalamic orexigenic peptides,which may be an important contributing factor to weight regain after the energy restricted diet.