Islets of patients with type 2 diabetes have the feature of an inflammatory process reflected by the presence of cytokines, immune cells, β-cell apoptosis, amyloid deposits and fibrosis. Indeed, β-cells from patients with type 2 diabetes display inflammatory markers including increased interleukin-1β expression and decreased IL-1 receptor antagonist. Furthermore, increased islet-associated macrophages are observed in human type 2 diabetic patients. These immune cells are most likely attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1β. There is also increasing clinical evidence that points to the role of elevated IL-1β in β-cell failure in patients with type 2 diabetes. Recent clinical studies using an IL-1 receptor antagonist and an anti-IL-1β antibody have shown improved glycemic control and β-cell function. Therefore, IL-1 antagonism appears as a new therapeutic approach to type 2 diabetes by targeting the master inflammatory cytokine triggering damage to insulin producing beta cells. It follows that modulation of intra-islet inflammatory mediators, in particular interleukin-1β, may prevent insulitis in type 2 diabetes and therefore presents itself as a possible causal therapy with disease-modifying potential.