The aim of the study was to evaluate whether the most common polymorphisms in the IL-6 and HSP70 genes affect the circulating heat shock protein 70 (HSP70), as well as inflammatory and prooxidant-antioxidant parameters in healthy men undergoing chronic endurance training. The subjects were randomly assigned to a 12-week swimming training (ST group) or control group (CON). Fasting blood samples were collected pre- and post-study period to assessment: superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, serum levels of lipid hydroperoxides (LHs), tumor necrosis factor α (TNFα), and HSP70. Subjects were genotyped for IL-6-174G/C, HSPA1A + 190 G/C and HSPA1B + 1538 A/G single nucleotide polymorphisms (SNPs) by real-time PCR. After a 12-week study period, a decrease in TNFα, HSP70, and GPx was observed in the ST group, but not the CON group. IL-6 SNP affected serum TNFα levels (main effect of genotype). Higher TNFα levels (pre- and post-study period) was observed in CC CON than in other IL-6 genotypes of CON and ST groups. However, a post-training decrease in TNFα was observed in both GG and CC IL-6 genotypes of ST group. In turn, only GG IL-6 genotype of the ST group was related to a post-training decrease in HSP70 (main time and genotype interaction). Moreover, pre- and post-training LHs were lower in GG than GC/CC HSPA1A genotypes of the ST group (main genotype effect). In conclusion, polymorphisms within the IL-6 and HSPA1A genes seem to affect baseline levels of some inflammatory parameters and prooxidant-antioxidant status and/or their changes after chronic swimming training. However, the results should be confirmed in a study with a larger sample size, one that includes individuals with sedentary lifestyles.