In this study, we investigated chemical structure of lycium barbarum polysaccharides and its modulatory effect on oxidative stress in high-fat mice. The polysaccharides mainly contained xylose and glucose. Little amount of rhamnose, mannose and galactose was observed. The lycium barbarum polysaccharides had IR bands at 800–1200cm −1 , 1450–1800cm −1 , 2500–3000cm −1 , and 3200–3600cm −1 , which were distinctive absorptions of polysaccharides. Rats are fed with high-fat diet for 2 months. Results showed that blood and liver antioxidant enzymes activities and GSH level in model mice significantly decreased, and MDA level significantly increased (P<0.01) compared to normal control mice. Administration of lycium barbarum polysaccharides significantly increased antioxidant enzymes activities and decreased MDA level in mice (P<0.01) compared to model group.