Objectives: This study aimed to investigate the cytokine response to acute endurance exercise performed in the lower body positive pressure treadmill (LBPPT) and to compare it with the regular treadmill. Materials and Methods: Eleven healthy physically active men aged between 18-22 years participated in the study. All subjects performed 45 minutes of running exercise at 70% maximal oxygen consumption (VO2max) on the regular treadmill and LBPPT in random order, one week apart. Blood samples were collected at pre-exercise, immediately post-exercise, 30 min post-exercise, and 2 h post-exercise to analyze serum high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-8 (IL-8) levels. Results: On the regular treadmill, hs-CRP levels were higher immediately, 30 min, and 2 h post-exercise than pre-exercise. In addition, it was lower 2 h post-exercise compared with immediately, and 30 min post-exercise. No significant differences in LBPPT for hs-CRP were observed for any time point. Hs-CRP concentration immediately and 30 min post-exercise was lower in the LBPPT than in the regular treadmill. TNF-α and IL-8 levels were unchanged in response to exercise performed neither on the regular treadmill nor on the LBPPT. Conclusion: Acute endurance exercise induces a limited systemic inflammatory response in physically active men.