This experiment was conducted to verify whether one time feeding of Lythrum salicaria root crude extract (LSR extract) exhibits liver protecting activities in acutely ethanol administrated rat. Experiment groups were composed of normal, negative control (alcohol control), 2 positive control (Hovenia dulcis extract 900 mg/kg and milk thisle 100 mg/kg), betulinic acid (20 mg/kg), a compound separated from LSR, and 3 LSR (100, 300, 900 mg/kg) groups. LSR treated groups showed decrease (p < 0.05) in serum triglyceride by dose-dependent manner. The content of serum albumin and the activity of ADH and ALDH in LSR extract fed rats were increased (p < 0.05) dependently on the administration amounts. Our study indicated that one time supplement of LSR downregulates oxidative stress and shows liver protective activity in the acute alcohol-fed rats.