Huyou(Citrus changshanensis)fruit is high in nutritional and medicinal value.Effects of different Huyou fruit tissues on glucose consumption in HepG2 cells and their hypolipidemic and hypolipidemic activity in vivo were investigated.Results showed that all the four parts of Huyou fruit,i.e.flavedo,albedo,segment membrane(SM)and juice sacs(JS),significantlyincreased glucose consumption in HepG2 cells in a dosedependent manner.Naringin and neohesperidin were isolated and characterized as two important bioactive compounds contributing to such glucose consumption activity in the cells.Western blot analysis suggested that the enhancement effect of naringin and neohesperidin on glucose consumption was associated with the phosphorylation of AMP-activated protein kinase,which was similar to that of metformin,a common hypoglycemic drug.By using the high-fat diet C57BL/6 mice and the diabetic KK-Ay mice,Huyou fruit extracts showed significantly hypoglycemic and hypolipidemic activities in vivo.In both animal models,decreased fasting glucose,serum glucose levels and elevated oral glucose tolerance as well as increased insulin sensitivity were observed.In addition,Huyou fruit extracts significantly decreased serum triglycerides(TG),total cholesterol(TCH),and leptin level.Our results showed that Huyou fruit may have the potential efficacy for prevention of diabetes and its complications.