Abstract: The model mice was established by feeding a diet of high-fat high-sucrose diet ( HFSD) .The aim of the present study was to unravel the effects of fucosylated chondroitin sulfate from Cucumaria frondosa ( Cf-CHS) on hyperglycemic effects and insulin resistance improvement in insulin resistant mice. Male C57BL /6 mice were randomly assigned into the normal control ( standard diet) , model control ( HFSD) , positive control ( HFSD +rosiglitazone ( RSG) , 1mg· ( kg·d) - 1) , Cf-CHS ( HFSD + + Cf-CHS, 80mg· ( kg·d) - 1) , Cf-CHS + RSG ( HFSD + Cf-CHS + RSG, 80 + 1mg· ( kg·d) - 1) groups. All animals fed with diet and water freely for 19 weeks. After experiments, the white fat weight, fasting serum glucose, serum insulin, serum adiponectin, resistin, leptin, and tumor necrosis factor- α ( TNF- α) levels were determined. Results showed that Cf- CHS markedly decreased fat deposition ( p < 0.01) , blood sugar ( p < 0.01) and insulin ( p < 0.05) levels, ameliorated insulin resistance ( p < 0.05) , increased serum adiponectin concentration ( p < 0.05) , and lowered serum resistin ( p < 0.01) , leptin ( p < 0.01) , TNF-α ( p < 0.05) levels.The effect was more significant when Cf- CHS compounded with RSG ( p < 0.05, p < 0.01) .Cf-CHS significantly decreased blood glucose level and ameliorated insulin resistance in insulin resistant mice, and the mechanisms may involved the regulation of adipocytokines parasecretion caused by adiposity.