We evaluated whether Monascus-fermented soybean extracts (MFSE) enriched with bioactive mevinolins (natural statins) and aglycone isoflavones (daidzein, glycitein, and genistein) perform an additive hypolipidemic effect in hyperlipidemic rats than unfermented soybean extracts (UFSE), which have a higher level of glucoside isoflavones (daidzin, glycitin, and genistin) without mevinolin. The oral administration of MFSE (200 and 400 mg kg(-1) body weight) significantly lowered the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels (p < 0.01) and raised high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05) in hyperlipidemic rats. The MFSE group had a significantly lower 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity and higher atherogenic index (calculated as HDL-C/LDL-C) when compared with the UFSE group (400 mg kg(-1) body weight) (p < 0.05). Treatment with both MFSE200 and MFSE400 groups for 40 days significantly reduced the activities of serum aspartate aminotransferase and alanine aminotransferase by averages of 35.6 and 43.2%, respectively, as compared to the high-fat diet group (p < 0.01). The results indicate that MFSE performs a more potent hypolipidemic action via improvement of the lipid profiles and down-regulated HMG-CoA reductase activity than UFSE in hyperlipidemic rats.