We assessed the effect of Se-methylselenocysteine (MSC) treatment, at a dose of 0.75 mg/rat/day for 1 or 2 weeks, on the activities of antioxidant systems in Sprague-Dawley rat tissues. Significant changes in glutathione and antioxidant enzyme activities, with different patterns among tissues, were evidenced. Glutathione content and its reduction state in the liver, lung, and kidney were elevated upon MSC treatment, whereas they were significantly lowered in the spleen. Among the tissues exhibiting glutathione increase, there were different enzymatic responses: $gamma$-glutamylcysteine ligase activity, the rate-limiting enzyme in the glutathione synthesis pathway, was increased in the liver, whereas the activities of the enzymes associated with glutathione recycling, namely, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase, were significantly increased in the lung and the kidney. The superoxide dismutase activity was decreased in all tissues upon MSC treatment, whereas catalase activity was increased in all tissues but the liver. Lipid peroxidation level was transiently increased at 1 week in the lung and the kidney, whereas it was persistently increased in the spleen. The increase was not evident in the liver. The results indicate that the MSC treatment results in an increase in the antioxidant capacity of the liver, lung, and kidney principally via an increase in glutathione content and reduction, which appeared to be a result of increased synthesis or recycling of glutathione via tissue-dependent adaptive response to oxidative stress triggered by MSC. The spleen appeared to be very sensitive to oxidative stress, and therefore, the adaptive response could not provide protection against oxidative damage.