Antrodia camphorata is a unique mushroom of Taiwan and has been used as a folk medicine for protection against liver damage induced by alcohol intoxication. However, no report has been presented in this respect. In this rat study, we examined whether the mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by ethanol (EtOH). Rats were orally administered with mycelium and sporocarp of Antrodia camphorata for 9 days before EtOH challenge (5.5 g/kg body wt., i.p.). Rats were divided into eight groups (A-H) and except for groups A and H, all rats were injected with alcohol. A: Control; B: EtOH control: C: Silymarin (250 mg/kg bw., p.o.); D: 0.5 g mycelium/kg; E: 1.0 g mycelium/kg; F: 0.5 g sporocarp/kg; G: 1.0 g sporocarp/kg; and H: 1.0 g mycelium/kg. The results showed that EtOH administration markedly increased the activities of glutamate-pyruvate aminotransferase (GPT) and glutamate-oxaloacetate aminotransferase (GOT). Both mycelium and sporocarp of Antrodia camphorata significantly decreased the activity of GOT and GPT, but the effects were not dose dependent. Mycelium and sporocarp of Antrodia camphorata also significantly and dose-dependently decreased lipid peroxidation (measured as TBARS) induced by EtOH. EtOH treatment significantly increased the activities of hepatic superoxide dismutase (SOD) and catalase, but did not significantly affect the activity of glutathione peroxidase. Pre-treatment with either the mycelium or the sporocarp completely prevented the rise in the activity of SOD and catalase. The histopathological examination revealed that both mycelium and sporocarp markedly protected against lipid vacuole accumulation and hydropic degeneration of hepatocytes induced by EtOH. Thus, the present results demonstrated that both mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by EtOH. In addition, rats fed 1.0 g mycelium without EtOH treatment produced no observable toxicity during the experimental period.