Aim. To evaluate the modifying effect of physical activity on the association of ADRB3, CLOCK, FABP2, FTO, PPARA, PPARD, PPARG, PPARGC1A, SHBG, UCP2 and UCP3 gene polymorphisms with body mass index (BMI), body fat mass, and risk of obesity. Subjects and methods. The investigation enrolled 582 students and 215 athletes who showed moderate and high physical activities, respectively. The students' body composition was estimated with a DIAMANT-AST bioimpedance analyzer. Gene polymorphisms were determined by polymerase chain reaction (PCR) or real-time PCR. Results. No differences in the rate of obesity risk alleles were found between normal-weight, and overweight or obese students. Correlation analysis in the total group of students revealed an association of the A allele of the FTO gene with BMI (р=0.0011) and body fat mass (р=0.0031). Comprehensive analysis summarizing the total number of obesity risk alleles for 7 polymorphisms of the PPARA, PPARD, PPARG, PPARGC1A, FTO, FABP2, and UCP2) genes in each individual showed that a subgroup of male students having a large number of obesity risk alleles (4-9) had higher BMI (22.6±2.73 kg/m2) than that of students having a small number of obesity risk alleles (20.8±2.81 kg/m2; р=0.0209). This pattern was not observed in the group of athletes regardless of gender and sports specialization. Conclusion. This investigation has demonstrated that physical activity has modifying effects on individuals who are genetically predisposed to obesity. Moderate and high physical activity considerably reduces the risk of obesity even in the presence of genetic risk factors.