The aim of this study was to test the effects of Ilex kudingcha total saponins on hemorheology of ApoE-/- mice suffering from hypercholesterolemia induced by high-cholesterol diet. The mice were randomly divided into six groups: the control group, the high-cholesterol diet group, 50 mg/kg atorvastatin treatment group, 75, 150 and 300 mg/kg Ilex kudingcha saponins treatment groups, and all the drug treatment groups were fed with a high-cholesterol diet. After administration with saponins (150 mg/kg or more) and atorvastatin (50 mg/kg) for six weeks, the plasma total cholesterol (TC), whole blood viscosity (WBV), plasma viscosity (PV), and erythrocyte aggregation index (EAI) had a remarkable decrease compared with that of the high-cholesterol diet group, but the hematocrit (Hct) and erythrocyte deformation index (DI) had no significant changes. In addition, it is found that the improving effects of saponins on reducing plasma fibrinogen (Fg) levels and prolonging the blood coagulation times including activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). In conclusion, the Ilex kudingcha total saponins may have a significant therapy application of hypercholesterolemia and atherosclerosis by considering its actions on hemorheological characteristics.