Type 2 diabetes mellitus (T2DM) is the most common form of diabetes. The association of low interleukin (IL)-10 production capacity with the metabolic syndrome and T2DM was recently established. Approximately 75% of the variation in IL-10 secretion capacity in humans derives from genetic factors that contribute to disease susceptibility. Based on the facts that IL-10 secretion ability is tightly controlled at the transcription level and the low production capacity of IL-10 is associated with T2DM, it seemed tempting to investigate if polymorphisms in the IL-10 gene promoter contribute to T2DM. IL-10 promoter polymorphisms at positions -592 and -819 among 370 consecutive patients with T2DM seen at the Department of Internal Medicine, Chung Shan Medical University Hospital, were examined using polymerase chain reaction restriction fragment length polymorphism. Though no significant association was detected between either the A-592C (p=0.088) or T-819C (p=0.160) polymorphism and T2DM, significantly more T2DM subjects carried -592*C (34.28%, p=0.027) and -819*C (32.57%, p<0.001) alleles, which were associated with high levels of IL-10 production. Nevertheless, no association was observed between these two polymorphisms and biochemical markers for T2DM. Our study suggests that IL-10 genetic polymorphisms may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of diabetes.