Objective: This study was conducted to investigate the hypolipidemic effect of the polysaccharide isolated from Pholiota nameko (PNPS-1). Methods: Hyperlipidemic Wistar rats were treated with PNPS-1 (20, 40, and 60 mg/kg orally) Results: Treatment of hyperlipidemic Wistar rats with PNPS-1 led not only to significant decreases in very low-density lipoprotein/low-density lipoprotein cholesterol (-48 98% and 21 54%, 40 and 60 mg/kg), triacylglycerol (-19 70%, -17.17%, -32.32%). phospholipids (-9.90%, -19.80%, -27.08%), and consequently the atherogenic index (23 61%, 70 42%, 82.85%) and a increase in high-density lipoprotein cholesterol (69.01% and 73.35%, 40 and 60 mg/kg) in serum, but also to significant decreases in total lipids (-10 24% and 33 16%, 40 and 60 mg/kg), total cholesterol (-24.22%, -34 26%, -55.02%), triacylglycerol (-22.53% and -38.50%, 40 and 60 mg/kg), and phospholipids (-27 41%, 60 mg/kg) in the liver. Further, PNPS-1 significantly suppressed lipid peroxidation by decreasing malondialdehyde and increasing antioxidant enzymes in serum (malondialdehyde, 9.94%, -22.22%, -32 75%, superoxide dismutase, 37.26%, 101%, 114%, catalase, 32.2%, 30.02%, 36 74%, glutathione peroxidase, 31.30%, 35.56%, 52.34%) of the 20-, 40-, and 60-mg/kg PNPS-1 groups and in the liver (malondialdehyde, -32.26%, -47.85%, catalase, 97%, 117%, glutathione peroxidase, 70 70%, 78.03%) in the 40- and 60-mg/kg PNPS-1 groups (superoxide dismutase, 24 35%, 67.49%, 234%). PNPS-1 was also effective in lowering body weight and some visceral weights (liver, heart, and kidney) in treated rats, except for the lung. PNPS-1 also ameliorated the pathologic changes in coronary arteries of hyperlipidemic rats. Conclusion: These results suggested that PNPS-1 significantly suppresses the development of hyperlipidemia and might be used as a potential therapeutic agent for hyperlipidemia. Crown Copyright (C) 2010 Published by Elsevier Inc All rights reserved.