Polysaccharide krestin (PSK) is a protein-bound polysaccharide extracted from the sporophore Coriolus versicolor. Previously, we found that PSK could reduce the oxidative injury that oxidised low-density lipoprotein (Ox-LDL) produced in monocytes/macrophages, and therefore have some pro-phylactic or therapeutic effect on atherosclerosis. Glutathione peroxidases, including selenium-dependent glutathione peroxidase (SeGPx) and non-selenium-dependent glutathione peroxidase (non-SeGPx, also called glutathione S-transferase [GST]), play an important role in the defence against oxidative injury. In order to find out if the effects of PSK were associated with antioxidant enzymes, we investigated its effect on glutathione peroxidase activity and messenger RNA (mRNA) expression in mouse peritoneal macrophages. Results showed that PSK enhanced SeGPx and non-SeGPx activity, and increased SeGPx and GST-P (pi class GST) mRNA in mouse peritoneal macrophages. In addition, the induction by PSK of the two glutathione peroxidases could be blocked by cycloheximide (30 micrograms/mL), but 5 micrograms/mL actinomycin D and 50 micrograms/mL acetovanilone (a superoxide inhibitor) had no effect. We conclude that PSK improved glutathione peroxidase activity through transcriptional induction of mRNA expression.