Type 1 diabetes (T1D) is a complex autoimmune disease that is untimely caused by the destruction of insulin-producing pancreatic β-cells by autoreactive T cells. The development of the pathology involved several cell types of both the innate and adaptive immune systems. This disease is under the control of several genetic loci of susceptibility but it is also influenced by environmental factors such as infectious agents. Studies in animal models, such as the non-obese diabetic (NOD) mouse, reveal that during the development of T1D multiple interactions occur between macrophages, dendritic cells (DC), natural killer (NK) cells, NKT cells, and lymphocytes. As a consequence, the various components of the immune system can be of peculiar interest as therapeutic targets for disease prevention or cure. This review focuses on the involvement of innate immune cells in the development and the prevention of T1D.