At lower concentrations, reactive oxygen species (ROS) serve as messenger molecules and regulate cellular adaptations. Uncontrolled oxidative stress, a state where the increased production of ROS overwhelms endogenous antioxidant protection may result in damage of lipids, proteins and genome. The contemporary definition of oxidative stress accounts the disruption of redox circuits leading to perturbation of redox control of signalling and cellular events. The heat shock proteins (HSPs), originally identified as heat-inducible gene products, are a highly conserved family of proteins that respond to a wide variety of stress including oxidative stress. HSPs function primarily as molecular chaperones, facilitating the folding of other cellular proteins, preventing protein aggregation, or targeting improperly folded proteins to specific pathways for degradation. Our in-vivo and in-vitro studies showed that increased oxidative stress and oxidative damage byproducts including 4-hydroxynonenal induce HSP expression. On the other hand, physiologically elevated HSP levels provide an extra protection against oxidative stress. Endurance training up-regulates HSP expression and may enhance the defense against oxidative stress. Disease conditions including diabetes may increase susceptibility to oxidative damage and impair HSP protection via transcriptional or post-translational mechanisms. Our results showed that endurance training may offset some of the adverse effects of diabetes by up-regulating tissue HSP expression.