Iron overload is one of the most common metal related toxicity. Under this circumstance, excessive iron deposition in liver will lead to further injury such as hepatocellular necrosis, inflammation, fibrosis, and in some cases even to carcinoma. In this paper, the effect of a nature flavonoid, baicalin, on iron overload-induced mouse liver oxidative injury has been studied. It was found that when iron-dextran-induced iron overload, mice were fed baicalin-containing diet (0.25% and 1%) for 50 days, hepatic iron, liver-to-body weight ratio, and hepatic lipid peroxidation were dose-dependently decreased; while catalase activity, total antioxidant status, and serum iron content were dose dependently increased. The protective effect of baicalin on liver of iron overload mouse may due to both the antioxidant and iron chelation activities of baicalin. These data provide preliminary experimental support for baicalin as medicine for iron overload diseases.