The aim of this study was to investigate the pharmacological effect of polysaccharides from Lentinus edodes on serum oxidative status and expression of VCAM-1mRNA of thoracic aorta endothelial cell in high-fat-diet rats. Forty male rats received two different diets during 40 days: standard chow (SC) and high-fat-diet (HF). The result indicates that the administration of polysaccharides from L. edodes significantly reduced serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c) and enhanced serum antioxidant enzyme activity and thymus and liver index in high-fat rats. In addition, the administration of polysaccharides from L. edodes significantly decreased the increased expression level of VCAM-1mRNA in group (V) (P<0.05). In conclusion, our data suggest that the administration of polysaccharides from L. edodes could decrease the increased oxidation stress induced by high-fat-diet and decrease expression of VCAM-1mRNA of thoracic aorta endothelial cell in rats.