Hyperlipidemia is one kind of common and frequently occurring syndromes and closely related to cardiovascular and cerebrovascular disease occurrences in the world. It is significant to explore the marine foods and potential drug resources for the application in treating the hyperlipidemia. We conducted this study to investigate the reducing effect and mechanism of kelp (Saccharina japonica) on serum lipid of rat models with hyperlipidemia induced by a fat-rich diet. The levels of serum lipid including the triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were detected by biochemical assay. Enzyme-linked immunosorbent assay was applied to determine the level of oxidized LDL (ox-LDL). The activity of lipoprotein lipase (LPL) and hepatic lipase (HL) was determined by chemical colorimetry. The concentrations of malondialdehyde (MDA) and nitric oxide (NO) were respectively measured by thiobarbituric acid assay and nitrate reductase assay. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were respectively determined by xanthinoxidase assay and chemical colorimetry. The results showed that the serum levels of TG, TC and LDL decreased, while HDL increased significantly in treated group compared with those of model groups (P < 0.05). The value of ox-LDL of treated groups was much lower than that of model groups (P < 0.05). The activities of LPL and HL in serum and hepatic tissue in treated groups were significantly higher than those of model groups (P < 0.05). The levels of MDA and NO in serum and hepatic tissue were lower than those of model groups (P < 0.05), while the activities of SOD and GSH-PX were significantly higher than those of model groups (P < 0.05). Our study indicated that kelp may correlate with the metabolism of TG, TC, LDL and HDL by enhancing the activities of LPL and HL, and regulate the levels of serum lipids by increasing the activities of SOD and GSH-PX to reduce the levels of MDA and NO.