Low-grade tissue inflammation induced by obesity can result in insulin 
resistance, which in turn is a key cause of type 2 diabetes mellitus. Cells of 
the innate immune system produce cytokines and other factors that impair insulin 
signalling, which contributes to the connection between obesity and the onset of 
type 2 diabetes mellitus. Here, we review the innate immune cells involved in 
secreting inflammatory factors in the obese state. In the adipose tissue, these 
cells include proinflammatory adipose tissue macrophages and natural killer 
cells. We also discuss the role of innate immune cells, such as 
anti-inflammatory adipose tissue macrophages, eosinophils, group 2 innate 
lymphoid cells and invariant natural killer T cells, in maintaining an 
anti-inflammatory and insulin-sensitive environment in the lean state. In the 
liver, both Kupffer cells and recruited hepatic macrophages can contribute to 
decreased hepatic insulin sensitivity. Proinflammatory macrophages might also 
adversely affect insulin sensitivity in the skeletal muscle and pancreatic 
β-cell function. Finally, this Review provides an overview of the mechanisms for 
regulating proinflammatory immune responses that could lead to future 
therapeutic opportunities to improve insulin sensitivity.