The ability of the β-cells to control blood glucose levels depends on their function and mass. In both, type 1 and type 2 diabetes mellitus the main processes leading to β-cell failure are apoptosis and loss of function. Many studies demonstrate how cytokines and chemokines have an active role in triggering the immune-response against the β-cell population. In a recent study we have identified that the chemokine CXCL10 may play an active role in triggering β-cell destruction. We have identified the Toll like receptor 4 as the receptor for CXCL10 and as new pathway for the induction of β-cell apoptosis. Our findings may open new therapeutic approaches to fight onset and progression of the disease.