Recent studies have demonstrated that gene expression is regulated not only by protein-coding genes, but also by nonprotein-coding small RNA molecules, microRNAs (miRNAs). miRNAs have emerged as important regulators involved in many biological processes, including cell proliferation and differentiation, apoptosis and metabolism and disease development. Here we report that specific miRNA deficiency in pancreatic islet cells exacerbates multiple low-dose streptozotocin-induced murine autoimmune type 1 diabetes, suggesting that miRNAs expressed in islet beta cells regulate their susceptibility to immune-mediated beta cell destruction.