The effect of Monascus purpureus red mould rice (RMR) on modulation of lipid metabolism and oxidative stress was studied in hypercholesterolemic rats. Cholesterol feeding for 14 weeks caused a significant increase in the lipid peroxides and total thiols and antioxidant enzymes, viz. glutathione peroxidase (GPx), glutathione reductase (GRd), superoxide dismutase (SOD) and catalase (CAT) in serum and liver in comparison to the control group. However, supplementation of RMR to hypercholesterolemic rats at 8, 12 and 16% significantly increased the GRd, GPx, SOD and CAT activities in serum and liver tissues. Furthermore, RMR feeding significantly decreased total thiols and lipid peroxides and also increased other antioxidant molecules such as glutathione and ascorbic acid in high-cholesterol fed rats. The efficiency of RMR (16%) in modulating the antioxidant molecules and antioxidant enzymes is comparable to standard drug-lovastatin. Thus, this study suggests that the long-term administration of RMR may play an important role in suppressing oxidative stress and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.