Ethyl pyruvate dissolved in a calcium-containing balanced salt solution--Ringer's ethyl pyruvate solution (REPS)--ameliorates ileal mucosal hyperpermeability and decreases the expression of several proinflammatory genes when it is used instead of Ringer's lactate solution (RLS) to resuscitate mice from hemorrhagic shock. Herein, we sought to determine whether delayed treatment with REPS would be beneficial in a murine model of acute alcoholic liver injury associated with binge drinking. Mice were gavaged with 3 doses of ethanol (5 g/kg each dose) over a 12-hour period and then randomized to treatment with 3 intraperitoneal doses of REPS or RLS over 12 hours. Compared with sham-treated controls not subjected to alcohol intoxication, RLS-treated mice demonstrated histologic evidence of fatty change and piecemeal necrosis of hepatocytes in the liver, as well as a significant increase in the plasma concentration of alanine aminotransferase. Biochemical changes induced by alcohol administration included increased hepatic lipid peroxidation, nuclear factor-kappaB activation, and tumor necrosis factor-alpha messenger RNA expression. All of these alcohol-induced effects were ameliorated by treatment with REPS instead of RLS. These data support the view that treatment with REPS ameliorates the hepatic inflammatory response and decreases hepatocellular injury in mice subjected to acute alcohol intoxication.