Dioxins are a class of polyhalogenated aromatic hydrocarbons that induces a wide spectrum of toxic responses in animals. In this study, two groups of Sprague-Dawley rats were exposed to 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD); one group received short-term exposure at a single dose of 1, 10, 20 or 50 microg/kg body weight and the other received long-term exposure to a daily low dose of 0.01, 0.1, 1 or 2.5 microg/kg body weight for one month. Two-dimensional electrophoresis was utilized to resolve the protein profile of rat plasma exposed to TCDD at different doses. One novel and three volume-increased spots were identified and characterized by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and electrospray-ionization on quadropole-TOF2 mass spectrometry. The novel protein was identified as plasma glutathione peroxidase precursor and the volume-increased proteins were cytokeratin 8 polypeptide, Ig lambda-1 chain C region and Ig lambda-2 chain C region. These proteins may be used as biomarkers to diagnose dioxin exposure and may help in understanding the toxic effects of dioxins.