Endurance exercise training can ameliorate many cardiovascular and metabolic disorders and attenuate responses to inflammatory stimuli. The purpose of this study was to determine whether the angiogenic and pro-inflammatory cytokine response to acute endurance exercise differs between endurance-trained and sedentary young men. Ten endurance-trained and ten sedentary healthy young men performed 30 min of treadmill running at 75 % VO2max with blood sampling before and after exercise. Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble VEGF receptor-1 (sFlt-1) were measured by multiplex ELISA. Acute exercise increased IL-6 by 165 % (P < 0.05), IL-8 by 32 % (P < 0.05), PlGF by similar to 16 % (P < 0.05), sFlt-1 by 36 % (P < 0.001), and tended to increase bFGF by similar to 25 % (P = 0.06) in main effects analyses. TNF-alpha and VEGF did not change significantly with exercise in either group. Contrary to our hypothesis, there were no significant differences in TNF-alpha, IL-6, VEGF, bFGF, PlGF, or sFlt-1 between groups before or after acute exercise; however, there was a tendency for IL-8 concentrations to be higher in endurance-trained subjects compared to sedentary subjects (P = 0.06). These results indicate that 30 min of treadmill running at 75 % VO2max produces a systemic angiogenic and inflammatory reaction, but endurance exercise training does not appear to significantly alter these responses in healthy young men.