Hypercholesterolemia and associated cardiovascular complications continue to occur in a great number of people. However, certain coastal populations have lower incidence of cardiovascular and other diseases, which may be attributed to regular intake of seaweeds in their diet. Seaweeds contain sulphated polysaccharides (SPS) which demonstrate a wide spectrum of biomedical properties and are phytochemical analogues of mammalian heparin sulphate. This knowledge served as the major impetus for exploring the therapeutic potential of SPS from the brown algae Sargassum wightii and SPS from Fucus vesiculosus in experimental rats against diet-induced hyperlipidemia and associated inflammatory complications. Adult male Wistar rats were divided into six groups with six rats in each. The control group (group I) was left untreated while group II rats were fed with a high cholesterol diet (CCT diet – normal rat chow with 4% cholesterol, 1% cholic acid and 0.5% thiouracil) for 14 days. Rats in groups III and IV received SPS from S. wightii (SW group) and SPS from F. vesiculosus (FV group) (5mg/kg b.wt/day, subcutaneously) during the last 7 days, respectively. Rats in groups V and VI were fed with a high cholesterol diet for 14 days and in addition were given SPS from S. wightii (CCT + SW group) and SPS from F. vesiculosus (CCT + FV group) at the weight of 5mg/kg b.wt/day, subcutaneously during the last 7 days, respectively. The adverse effects of hypercholesterolemia were evident from increased levels of serum lipid status and inflammatory complications manifested by augmented levels of plasma tumour necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase (COX-2) and lysosomal enzymes. Treatment with algal SPS considerably restored the above abnormalities. SPS from S. wightii and SPS from F. vesiculosus were almost equally effective in mitigating hypercholesterolemia and related inflammatory complications.