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Zembron-Lacny, A, Ziemann, E, Zurek, P, and Hübner-Wozniak, E. Heat shock protein 27 response to wrestling training in relation to the muscle damage and inflammation. J Strength Cond Res 31(5): 1221–1228, 2017—One of the unique features of an exercise is that it leads to a simultaneous increase of antagonistic mediators. On the one hand, exercise elevates catabolic proinflammatory cytokines. On the other hand, exercise stimulates anabolic components such as heat shock proteins (HSPs), which protect against stressors. Therefore, the study was designed to evaluate the blood level of HSP27 and its relationship with muscle damage and inflammatory mediators in elite Greco-Roman wrestlers during training periods differed in type and intensity exercise. Ten male wrestlers (21.2 ± 2.1 years) were observed during the conditioning camps at preseason (January), at the beginning of tournament season (April), and during tournament season (June). Twelve healthy and untrained men (19.2 ± 0.4 years) were considered a reference group. The serum levels of inflammatory mediators and HSP27 in wrestlers were significantly different from nonathletes. In wrestlers, reactive oxygen and nitrogen species H2O2, NO, and 3-nitro, cytokines interleukin-1β and tumor necrosis factor α, and also HSP27 reached the highest levels at preseason (January) or tournament season (June) when the special training predominated (>30% training load) over directed training (approximately 10% training load). Creatine kinase activity also demonstrated the highest level during the same training periods (January 2,315 ± 806 IU·L−1; June 3,139 ± 975 IU·L−1). The regression analysis revealed the relationship of HSP27 level with muscle damage (rs = −0.613, p < 0.001), and also with inflammatory mediators. The results of this study show that wrestling training modulates HSP27 level, which is significantly related with skeletal muscle damage and inflammatory response, and suggest that measure of HSP27 level can be useful diagnostic tool in biochemical assessment of athletes to increase their performance.