Experimental studies carried out for evaluating the anti-hyperlipidemic properties of rice bran components have given interesting but often contrasting results. Therefore, the current study was initiated to investigate the anti-hyperlipidemic activity of oryzanol (OZ), a commercially-important bioactive phytochemical, isolated from crude rice bran oil (cRBO). OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Subsequently, OZ (50 and 100 mg/kg, p.o.) was evaluated for anti-hyperlipidemic activity in Triton WR-1339-induced acute hyperlipidemic albino rats by estimating serum triacylglyceride (TG), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) levels with atorvastatin as the reference standard. The degree of protection was also assessed by measuring the levels of various hepatic anti-oxidant enzymes. OZ evoked a significant decrease in the levels of serum cholesterol, triacylglycerides, LDL, VLDL and a significant increase in the level of serum HDL and hepatic anti-oxidant enzymes. It also showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios. These findings indicate that OZ possesses the potential to lower plasma lipid concentrations and might be of therapeutic benefit in hyperlipidemia and atherosclerosis.