Objective: The hyperlipidemia rat model was established to study the hypolipidemic effect of compound kelp meal substitute powder rich in dietary fiber and unsaturated fatty acids. Methods: Male SD rats were divided into blank control group, model control group and high, medium and low dose groups: 6.58, 3.29 and 1.65 g/kg (equivalent to 10, 5 and 2.5 times of the recommended dose of human body respectively). The blank control group was fed with basic diet, and the other groups were fed with high-fat diet, and the three dose groups were given the corresponding concentration of compound kelp powder suspension by gavage. After four weeks of continuous intragastric administration, the serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the atherosclerosis index (AI) was calculated. Results: The three doses of compound kelp powder could reduce serum TC (low dose group P＜0.05, medium and high dose group P＜0.01), TG (P＜0.05) and LDL-C level (low dose group P＜0.05, medium and high dose group P＜0.01), and increase HDL-C level (medium and high dose group P＜0.01) showing dose-dependent. Moreover, it could effectively inhibit the increase of atherosclerotic index in hyperlipidemic rats (P＜0.01). Conclusions: Compound kelp meal substitute powder had a good effect on reducing blood lipid and anti-atherosclerosis.