High-fat diet (HFD) feeding in mice is characterized by accumulation of αβ T cells in adipose tissue. However, the contribution of αβ T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of αβ T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFNγ+ (T H 1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity.Mice lacking αβ T cells (T cell receptor beta chain-deficient [TCRb−/−] mice) were fed HFD for 12 weeks. Obesity-induced skeletal muscle and adipose tissue inflammation was assessed by flow cytometry and quantitative RT-PCR. To investigate the effect of T H 1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5 × 10 5 T H 1 cells or PBS weekly over 12 weeks into HFD-fed TCRb−/− mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with T H 1-conditioned medium.We showed that similar to adipose tissue, skeletal muscle of obese mice have higher αβ T cell content, including T H 1 cells. TCRb−/− mice were protected against obesity-induced hyperglycemia and insulin resistance. We also demonstrated suppressed macrophage infiltration and reduced inflammatory cytokine expression in skeletal muscle and adipose tissue of TCRb−/− mice on HFD compared to wild-type obese controls. Adoptive transfer of T H 1 cells into HFD-fed TCRb−/− mice resulted in increased skeletal muscle and adipose tissue inflammation and impaired glucose metabolism. T H 1 cells directly impaired functions of C2C12 myotubes and 3T3-L1 adipocytes in vitro.We conclude that reduced adipose tissue and skeletal muscle inflammation in obese TCRb−/− mice is partially attributable to the absence of T H 1 cells. Our results suggest an important role of T H 1 cells in regulating inflammation and insulin resistance in obesity.