The association of T helper (Th) 1 cells with obesity is well documented in both animals and humans. The T-box transcription factor (T-bet) is known as the transcription factor that is responsible for the development of Th1 cells. However, the role of T-bet in obesity has never been elucidated. The present study aimed to investigate the regulatory function of T-bet on obesity in mice. Th1 cytokine levels were decreased, whereas Th2 cytokine level and GATA-3 messenger RNA (mRNA) expression were increased in T-bet knockout (KO) mice. T-bet KO male mice induced obesity as a result of increased body weight and food efficiency despite the fact that they feed a control diet. T-bet KO mice have an increase in weight of white adipose tissue and levels of triacylglyceride and low-density lipoprotein cholesterol. Interestingly, the expression levels of energy expenditure-related genes were decreased in T-bet KO mice. Both T-bet KO male and female mice had impaired glucose tolerance. In white adipose tissue, leptin, the increase in peroxisome proliferator receptor-γ and CAAT/enhancer-binding protein α mRNA expressions in T-bet KO mice was more than that in wild-type mice. Furthermore, we found that the level of interleukin (IL)-6 mRNA expression in white adipose tissue was elevated in T-bet KO mice but not IL-1β and tumor necrosis factor-α. IL-6 mRNA expression was increased in adipocyte fraction and stromal vascular fraction in white adipose tissue of T-bet KO mice. Taken together, our results reveal that T-bet may affect obesity through the regulation of IL-6 expression in adipocytes of white adipose tissue.