The anti-hyperlipidemic effects of an ethyl acetate fraction from Orostachy japonicus in a high lipid diet-induced hyperlipidemic rat model were assessed. The fraction, which contained kaempferol, astragalin, and isoquercitrin, was associated with significant weight loss and reduction of lipid contents in serum and liver tissues. The fraction, which contains mainly flavonoids, diminished the levels of malondialdehyde and hydroxyl radical, and increased the anti-oxidative enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Reduced bleeding and plasma clotting times resulting from the administration of the ethyl acetate fraction may reduce cardiovascular disease associated with hyperlipidemia.