In this study, we fermented sea tangle (FST) using Lactobacillus brevis BJ20, and its protective effect against the ethanol-induced hepatotoxicity in Sprague-Dawley rats was evaluated. Administration of ethanol to rats for 3 weeks induced liver damage with significant increase in hepatic malondialdehyde level and decrease in glutathione and antioxidant enzyme activities including catalase, superoxide dismutase and glutathione peroxidase. However, pretreatment of rats with FST inhibited the ethanol-induced oxidative stress in liver by suppressing the lipid peroxidation, and maintained the levels of antioxidant enzymes as well as glutathione. Further, FST markedly decreased the lipid peroxidation in many vital organs such as kidney, heart, microsome, mitochondria, testis and spleen of rats. The biochemical changes were consistent with histopathological observations indicating marked hepatoprotective effect of FST. Hence, these results suggested that the FST exhibit potent hepatoprotection against the ethanol-induced oxidative stress in rats.