Loss of beta cell mass and function contributes to the onset of overt diabetes. Activation of the JNK-signalling pathway is associated with beta cell failure, apoptosis and diabetes. Some data shows TNFα-receptor associated factor 2 (TRAF2) mediates JNK pathway activation. Therefore, we predicted that genetic deletion of TRAF2 in beta cells would improve beta cell function and prevent diabetes. To test this idea, we generated 'bTRAF2' mice by crossing TRAF2-"floxed" mice with RIP.CRE mice. TRAF2 protein expression, while abundant in primary islets and beta cell lines, was reduced by >85% in bTRAF2 islets. When stimulated with TNFα, bTRAF2 islets showed a marked delay in the kinetic of JNK phosphorylation, followed by profoundly prolonged phosphorylation of JNK. In contrast, TNFα-stimulated activation of NF-kB and p38 pathways proceeded normally. siRNA-mediated silencing of TRAF2 in MIN6 cells resulted in delayed JNK phosphorylation and normal NF-kB and p38 activation. Altered JNK kinetics correlated with hyper-expression of JNK-regulated genes CXCL10, ICAM1 and TNFα. bTRAF2 and control mice were fed a high-fat diet starting at 8 weeks-of-age and subjected to i.p. glucose tolerance tests (ipGTT) after 4 and 8 weeks. Chow-fed bTRAF2 mice showed a trend for poorer glucose tolerance, which worsened with age, suggesting TRAF2 is required for normal glucose tolerance. On a high-fat diet bTRAF2 mice exhibited exacerbated glucose intolerance compared to controls. To determine if this was a beta cell specific defect, hand-counted bTRAF2 islets were transplanted into syngeneic, diabetic recipients. Here, mice receiving bTRAF2 islets displayed erratic control of blood glucose levels. When challenged by ipGTT bTRAF2 islet recipients showed poor glucose tolerance compared to controls. Contrary to expectations, TRAF2 controls the cellular tempo of JNK activation in beta cells rather than its activation per se. Thus, appropriate activation of JNK is necessary for maintaining glucose tolerance in a diabetic milieu.