Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B), an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl 4 ) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1,3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl 4 -treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl 4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl 4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.