ObjectiveThe production of interleukin (IL)-29 andthe genes related to IL-29 signaling pathway (STAT1, NF-κB, and NFATc1), and T helper (Th) 1 cells (T-bet, IFN-γ, TNF-α, and IL-2) were evaluated in type 2 diabetes mellitus (T2DM). Correlations between IL-29 and diabetes parameters, and between gene expression in IL-29 pathway and Th1 cells were also examined. Materials and Methods41 newly diagnosed patients with T2DM and 41 healthy controls were recruited. CD4+ T cells were purifed and the production of IL-29 in the supernatant of anti- CD3 and anti- CD28 activated Th cells was detected using ELISA. The expression of IL-29- and Th1- related genes was determined with real-time PCR. ResultsThe secretion of IL-29 and the expression levels of NF-κB, NFATc1, IFN-γ, and TNF-α in Th cells were seen to be increased in diabetes persons compared to controls. Positive connections between IL-29 with hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were found in diabetes persons. IL-29 was positively correlated with NFATc1 and TNF-α. NFATc1 was positively related to TNF-α. ConclusionAbnormal expression levels of IL-29- and Th1- related genes are linked with T2DM pathogenesis. IL-29 may amplify the expression of Th1-specific genes especially TNF-α by upregulating NFATc1 expression.