The bile acid-responsive G protein-coupled receptor TGR5 has been shown to control critical metabolic functions and its activation confers protection against several metabolic-related diseases, including diet-induced obesity, liver steatosis, atherosclerosis and insulin resistance. TGR5 is expresseds in several cell types including macrophages, which are responsible for the activation of inflammatory processes that can affect nearby metabolic organs such as the adipose tissue. In the present work we aimed to evaluate the effect of TGR5 activation in the control of inflammation and insulin resistance in the adipose tissue. For this purpose, we used bone-marrow chimeric mice lacking leukocyte TGR5 and macrophage-specific TGR5 mutant mice. We observed that obese mice lacking macrophage TGR5 develop exacerbated adipose tissue inflammation and insulin resistance along with increased chemokine expression and macrophage number. Conversely, pharmacological activation of TGR5 markedly decreased LPS-induced chemokine expression in primary macrophages and this effect was mediated by mTORC1/CEBPb-LIP pathway. In conclusion, these studies reveal a TGR5 downstream signaling pathway, which could be used in the prevention of chronic inflammatory diseases and type 2 diabetes mellitus.