We have demonstrated that in rats subjected to partial hepatectomy (PH), the regenerating liver had an enhanced metabolism of ethanol, which largely depended on the route and timing of ethanol administration. Therefore, the influence of the administration route and timing for ethanol-induced deleterious effects on the regenerating rat liver was evaluated in animals subjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion of hepatocellular structure, and high mitotic index. Intragastric ethanol administration (1.5 g/kg body weight) considerably reduced the PH-induced changes in liver structures. Ethanol treatment also decreased liver thymidine kinase activity, serum albumin, and glucose levels. Intraperitoneal administration of the same ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of its administration route, ethanol abruptly shortened a PH-induced selective increase in serum enzyme activities. These data suggest that the inhibitory effect of a low dose of ethanol on PH-induced liver regeneration is dependent on the timing and route of administration.