ABSTRACT Introduction Fast population aging is a global reality. Today’s major challenge is to promote the healthy aging of more and more people by acting on factors that can be modified, such as physical exercise. Regular exercise could contribute to the prevention of chronic diseases associated with aging. Research has been conducted on the physical training response of elderly individuals, but there is not yet any consensus on the influence of strength training or IL-6 polymorphism on levels of inflammatory markers such as IL-6 and muscle damage marker CK, particularly in healthy elderly male individuals. Objectives The aim of this study was to evaluate the relationship of IL-6 promoter -174 C/G gene polymorphism on systemic IL-6 responses and muscle damage after eccentric strength training in elderly men. Methods This is a prospective, high-quality study. Gene frequency of polymorphism of promoter gene IL6 G-174C was identified using the Hardy-Weinberg test in 28 older male volunteers. The relationships of each genotype with IL-6 and CK serum levels were analyzed. CK and IL-6 levels were determined at pre-training and 0h, 3h, 24h, and 48h post-training periods. Results Differences in baseline and post-training IL-6 levels of genotypic groups were observed for all time periods analyzed (p = 0.029). Eccentric exercise efficiently reduced post-intervention muscle damage, thus showing a statistical difference between the pre- and post-intervention time points ( p = <0.0005). Conclusion Eccentric training influenced CK and IL-6 modulation independently of the polymorphism of the IL-6 promoter gene -174 C/G. Level of evidence II, Prospective comparative type.