Hyperlipidemia plays a vital role in cardiovascular disease, and threatens our lives. The aim of this paper is to study the effects of Shuanghua granules on blood lipid in normal mice and different hyperlipidemia models. Acute and endogenous hyperlipidemia was induced in mice with yolk and Triton WR-1339 respectively. The model of hyperlipidemia in rats was set up by feeding high cholesterol diet. Then preventive effects of Shuanghua granules was observed compared with lovastatin and Zhibituo. We found that Shuanghua granules 5.6, 11.3, 22.5 g x kg (-1) could significantly reduce the serum TG level in normal mice (P < 0.01, P < 0.05). No significant difference was found in liver index, serum TG and HDL-C levels. When the mice were treated with either yolk or Triton WR-1339 in the presence of Shuanghua granules, the plasma lipoprotein levels (TC and LDL-C) were significantly reduced (P < 0.01, P < 0.05). Shuanghua granules could reduce the serum TC, TG, LDL-C, MDA, NEFA and liver TC, TG, LDL-C levels, simultaneously raise serum and liver HDL-C, serum SOD, LPL, HL, LA levels of hyperlipidemia rats (P < 0.01, P < 0.05). Shuanghua granules also significantly reduced whole blood viscosity, RV, etaP, IER and IEA (P < 0.01, P < 0.05), and lowered fatty degeneration of liver tissue. Compared with hyperlipidemia model, there was no significant increase in faeces lipoids concentrations. The results confirmed the mechanism of blood lipid regulating effects of Shuanghua granules is probably related with its antioxidation, regulating hemorheology and improving LPA, HL, LA enzymatic activity.