Endotoxemia is a common event in alcoholic liver disease. Elevated intestinal permeability is the major factor involved in the mechanism of alcoholic endotoxemia and the pathogenesis of alcoholic liver disease. This study examined the effect of epigallocatechin-3-gallate (EGCG) on alcohol-induced gut leakiness, and explored the related mechanisms involved in its protection against alcohol-induced liver injury in rats. Four groups of female Sprague-Dawley rats were studied. Alcohol and alcohol/ EGCG groups rats received fish oil along with alcohol daily via gastrogavage for 6 weeks, and dextrose and dextrose/EGCG groups rats were given fish oil along with isocaloric dextrose instead of alcohol. The dextrose/EGCG and alcohol/ EGCG groups received additional treatment of EGCG (100mg.kg(-1) body weight) daily intragastrically by gavage. Intestinal permeability was assessed by urinary excretion of lactulose and mannitol (L/M ratio). Liver injury was evaluated histologically and by serum alanine aminotransferase (ALT). Plasma endotoxin and serum tumor necrosis factor-alpha (TNF-alpha) levels were assayed; liver malondialdehyde (MDA) contents determined. CD14 and inflammatory factors, such as TNF-alpha, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase ( iNOS) mRNAs in the liver were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rats given fish oil plus alcohol had gut leakiness (L/M ratio was increased), which was associated with both endotoxemia and liver injury. The above responses were accompanied by increased CD14, TNF-alpha, COX-2 and iNOS mRNA expressions in the liver. EGCG supplementation partly blocked the gut leakiness, reduced endotoxemia and lipid peroxidation, and blunted the elevated expressions of CD14, TNF-alpha, COX-2 and iNOS, all of which were associated with improved liver injury. These results show that EGCG can block alcohol-induced gut leakiness, reduce endotoxemia, and inhibit inflammatory factors expressions in the liver, thereby ameliorates alcohol-induced liver injury.