Islets of patients with type 2 diabetes have the feature of an inflammatory process reflected by the presence of cytokines, immune cells, beta-cell apoptosis, amyloid deposits and fibrosis. Indeed, beta-cells from patients with type 2 diabetes display inflammatory markers, including increased interleukin (IL)-1 beta expression. Furthermore, increased islet-associated macrophages are observed in human type 2 diabetic patients and in most animal models of diabetes. Importantly, increased numbers of macrophages are detectable very early in high fat-fed mice islets, before the onset of diabetes. These immune cells are most likely attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1 beta. It follows that modulation of intra-islet inflammatory mediators, in particular IL-1 beta, may prevent insulitis in type 2 diabetes and therefore presents itself as a possible causal therapy with disease-modifying potential.