Impaired antioxidant defense increases the oxidative stress and contributes to the development of type 2 diabetes mellitus (T2DM). MnSOD and eNOS are important antioxidant enzymes. This aim of this study was to verify the association of MnSOD and eNOS tagSNPs with T2DM in a Chinese Han population. Four tagSNPs of MnSOD and eight tagSNPs of eNOS were detected using TaqMan technology in 1272 healthy controls and 1234 T2DM patients. All study participants were unrelated members of the Han ethnic group in China.