Yerba Mate tea (Mate) is believed to be a natural source of cardioprotective lipid-lowering and antioxidant compounds. In this study, the antihyperlipidemic and antioxidant effects of Mate tea in a rat hyperlipidemia model were investigated. Male Sprague-Dawley rats were divided randomly into five groups and fed varying diets: standard diet, hyperlipidemic diet, and hyperlipidemic diet supplemented with low, moderate, or high concentrations of Mate tea aqueous extract (1%, 2%, and 4% w/v, respectively). Compared to the hyperlipidemic control group, Mate tea reduced significantly the total body weight and lowered serum levels of total cholesterol, triglyceride, and low-density lipoprotein-cholesterol, and caused the elevation of serum levels of high-density lipoprotein-cholesterol. Moreover, activities of superoxide dismutase and glutathione peroxidase in serum were elevated significantly, whereas the levels of malondialdehyde decreased. In addition, Mate tea treatment ameliorated significantly the severe fatty degeneration of liver cells that occurred in the hyperlipidemic groups. The relative levels of sterol regulatory element binding protein 1 and its target fatty acid synthase, as well as acetyl-CoA carboxylase mRNA transcripts were reduced, whereas peroxisome proliferator-activated receptor alpha mRNA transcripts were elevated in the Mate tea groups. Our results suggest that Mate tea exerts strong antioxidant and lipid-lowering effects, prevents hepatic fatty deposition, and regulates the expression of lipid metabolic regulators. It can therefore be used to reduce the risk of atherosclerosis. Copyright © 2012 John Wiley & Sons, Ltd.