Glycyrrhetinic acid (GA), which is a main active principal constituent of liquorice, is extensively used as antibacterial and anti-inflammatory Chinese medicine. This study was carried out to evaluate the effects of GA on the oxidative stress of Ictalurus punctatus injection lipopolysaccharide (LPS). The fish were randomly divided into two groups:a control group (fed a standard diet) and a treatment group (standard diet supplemented with 0.15 mg/kg GA) and fed for 8 weeks. We then challenged the fish with LPS and recorded changes in red and white blood cell counts (RBC and WBC), plasma cortisol, lysozyme, ACH50, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hepatic catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) for a period of 48 h. Supplementation with 0.15 g/kg GA significantly increased plasma lysozyme activity before infection, plasma ACH50 activity at 6 h after infection, WBC hepatic at 6 h after infection, CAT activity 24 h after infection, hepatic SOD activity before and after infection. In addition, the supplemented group had decreased levels of plasma AST and ALT activities 6 h after infection, hepatic CAT 3 h after infection, hepatic MDA 24 and 48 h after infection. Our results suggest that ingestion of a basal diet supplemented with 0.15 g/kg GA prevents LPS-induced immunological challenges response by regulating key enzyme activities, and challenged with LPS (2.0 mg/kg) affect physiological responses and immunoreactions of channel catfish.