The inhibitory effects of the traditional herbal medicine Dai-saiko-to (Da-Chai-Hu-Tang) on the progression of the atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control group and a Dai-saiko-to-treated group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (29.1%) and 26 (51.5%). This progression of atherosclerotic lesions did not happen in the Dai-saiko-to-treated group between week 12 (26%) and 26 (27.4%). Antioxidative effects on LDL were seen in the Dai-saiko-to-treated group in weeks 16 and 18. Dai-saiko-to did not improve the hypercholesterolemia in the KHC rabbits. These results suggest that Dai-saiko-to has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH model rabbits. It is possible that the antioxidative effects of Dai-saiko-to on LDL led to the beneficial effects observed in this study.