Diabetes exerts a negative impact on tissue protection through a number of mechanisms including impaired heat shock protein (HSP) defence. In insulin resistant states and diabetes, heat shock factor 1 (HSF-1) is low in insulin sensitive tissues, resulting in low HSP60, HSP 70 and HSP90 levels. Strategies to decrease oxidative stress and to modulate stress proteins: expression of heat shock proteins, which are important components of protein homeostasis and cell survival may have important implications for reducing insulin resistance, improving impaired glucose regulation and increasing the protection against diabetes and its complications. After the 2-years exercise-diet intervention oxidative stress was reduced as shown by decreased serum levels of uric acid and protein carbonyls in subjects with impaired glucose tolerance (IGT). In addition cytoprotection was improved in the skeletal muscle tissue, observed as the increased expression of mitochondrial HSP60 and GRP75 in the IGT subjects while no response was found in cytoplasmic chaperones HSP72 and HSP90. The adaptive changes in the expression of GRP75 and HSP60 could support mitochondrial protein import, protein folding and enhance tissue protection in insulin-resistant muscle tissue. These adaptive changes of mitochondrial HSPs and increased oxidative capacity are mainly due to increased contractile activity of skeletal muscle. Exercise has both direct and indirect positive effects on muscle and whole body metabolism. The benefits can be obtained at exercise levels, which are safe and possible in everyday life in middle aged subjects.