Oxidative stress induces a variety of cellular responses including proliferation and apoptosis. Cellular reduction/oxidation (redox) status is regulated by cellular thiols including gluthathione and thioredoxin (TRX). TRX is a small protein with a redox-active disulfide/dithiol within its active site sequence: -Cys-Gly-Pro-Cys- and operates together with NADPH and thioredoxin reductase as a protein disulfide reducing system. Human TRX was originally cloned as adult T cell leukemia-derived factor (ADF) produced by human T cell leukemia virus type-I (HTLV-I) transformed T cells. TRX is induced by oxidative stress and secreted from cells. Intracellular TRX is involved in the regulation of protein-nucleic acids interactions. Extracellularly, TRX shows cytokine-like activities such as growth promotion and cytoprotection against oxidative stress. There is collecting evidence indicating that the TRX system as well as the GSH system play a crucial role in the signal transduction of cellular responses and in the host defense system against oxidative stress.