Type 1 diabetes (T1D) arises as a consequence of autoreactive T cell-mediated destruction of pancreatic beta cells. The mechanism of beta cell killing in vivo, however, remains unclear. Using an in vivo reconstitution assay, we studied the mechanisms of beta cell death in a mouse model of T1D. Mouse islets with altered expression of critical cell death proteins were tested for their ability to survive the attack by diabetogenic T cells. Loss of individual BH3-only proteins Bim, Puma or Bid did not protect beta cells from this death. Furthermore, overexpression of the anti-apoptotic protein Bcl-2 or combined deficiency of the pro-apoptotic proteins Bax and Bak failed to prevent beta cell destruction. We also showed that inhibition of Fas and its downstream signalling molecule FADD in islets did not prevent diabetes. Apoptotic pathway is therefore dispensable for beta cell killing in T1D. Using electron microscopy we observed that dying beta cells showed features of necrosis. However, islets deficient in RipK3, a critical regulator of death receptor-induced necrosis, were susceptible to T cell-mediated destruction. Simultaneous inhibition of apoptosis and death receptor-induced necrosis by combining deletion of RipK3 and overexpression of Bcl-2 in islets did not protect against immune attack either. Collectively, our data indicate that necrosis is an important mechanism of beta cell death in T1D, and the death signal is transduced through a death receptor-independent mechanism.