IL-6 signaling usually occurs through a trans-membrane complex consisting of an IL-6 receptor-α (IL-6Rα) homo-dimer and gp130 receptor-β (gp130Rβ), but IL-6 may also signal by binding a soluble receptor (sIL-6R) termed “IL-6 trans-signaling”. We sought to determine whether IL-6 trans-signaling contributes to adipose tissue inflammation and insulin resistance in obesity. Sgp130Fc and littermate control (WT) mice were fed a chow or high fat diet (HFD) for 12 wk. The HFD increased fat mass equally when comparing sgp130Fc with WT mice. As expected, EmR1 mRNA expression in white adipose tissue (WAT), the percentage of adipocytes surrounded by macrophages (F4/80+ staining) in crown like structures and the percentage of macrophages in WAT staining positive for F4/80 and CD11c were all elevated in WT mice fed a high fat diet. Importantly, despite the equivalent fat mass compared with WT on HFD, no such increases in these measures of adipose tissue inflammation were observed in sgp130Fc mice. Next, we performed euglycemic hyperinsulinemic clamp experiments in one cohort of mice fed a HFD. These preliminary data demonstrated that the glucose infusion rate during the clamp was ~2-fold higher in sgp130Fc compared with WT mice, which was due to an enhanced glucose disposal rate, rather than alterations in the suppression of hepatic glucose production, during the clamp. These data demonstrate that blocking IL-6 trans-signaling can prevent adipose tissue inflammation and possibly attenuate insulin resistance in obese mice. Since sgp130Fc protein has been intended for use as a drug to treat human inflammatory bowel diseases, these data suggest that sgp130Fc may be a viable therapeutic treatment for human type 2 diabetes.