The focus of this review is to summarise the known relationships between the expression of Heat Shock Protein 60 (Hsp60) and its association with the pathogenesis of Type 1 and Type 2 Diabetes Mellitus. Hsp60 is a mitochondrial stress protein that is induced by mitochondrial impairment. It is known to be secreted from a number of cell types and circulating levels have been documented in both Type 1 and 2 Diabetes mellitus patients. The biological significance of extracellular Hsp60 however, remains to be established. We will examine the links between Hsp60 and cellular anti and pro- inflammatory processes and specifically address how Hsp60 appears to affect immune inflammation by at least two different mechanisms: as a ligand for innate immune receptors and as an antigen recognized by adaptive immune receptors. We will also look at the role of Hsp60 during immune cell activation in atherosclerosis, a significant risk factor during the pathogenesis of Diabetes Mellitus.