Programmed cell death protein 1, also known as PD-1 or CD279 is a protein expressed on T cells and pro-B cells. It is a cell surface receptor that belongs to the immunoglobulin superfamily. PD-1 is known to be the major inhibitory receptor that functions as an immune checkpoint, playing an important role in down regulating the immune system. Autoimmunity is an odd reaction of immune system to human antigens (autoantigens). The triggers leading to recognition of own determinants, receptors, surface molecular cellular antigens as ‘foreign’, followed by activation of T and B lymphocytes, are unknown. The genetic background seems to play a limited role. This autoimmune process include tissue infiltration with immunocompetent cells, overproduction of pro-inflammatory cytokines, and production of autoantibodies by plasmocytes. The increased prevalence of diabetes mellitus is considered one of the greatest public health diseases nowadays. Type 1 diabetes mellitus (T1DM), a polygenic autoimmune disease, is resulted from both genetic and environmental factors.