Postprandial lipemia (PPL) is associated with impaired endothelial function and inflammation. Acute exercise reduces PPL in adults. This investigation examined the effect of an acute bout of exercise on postprandial changes in triglycerides (TG), glucose, insulin, inflammation [white blood cell count (WBC), interleukin-6 (IL-6) tumor necrosis factor-alpha, C-reactive protein (CRP)] and endothelial activation [soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1)] following a high-fat meal in adolescents. Ten normal weight (NW) (BMI, 20.9 ± 1.7 kg m⁻²; 15.6 ± 0.7 years) and eight overweight (OW) (BMI, 28.3 ± 3.6 kg m⁻²; 15.9 ± 0.4 years) adolescent boys underwent two 6-h oral fat tolerance tests (OFTT) separated by 7–10 days. On the evening prior to each OFTT, subjects either rested or completed a treadmill exercise bout (65% [(V)\dot]\textO_2max ; \dot{V}{\text{O}}_{2\max } ; 600 kcal expended). Exercise reduced (P < 0.01) the postprandial TG area under the curve by ~20% in the NW and OW groups. The postprandial glucose and insulin response did not differ between the control and exercise trials or between the NW and OW groups. Circulating leukocytes and plasma IL-6 levels increased (P < 0.01) in the NW and OW groups 6 h following the OFTT in both experimental conditions. There were no changes in CRP, sVCAM-1 or sICAM-1 following the OFTT and there were no differences between experimental condition or NW and OW groups. In conclusion, a moderate exercise bout prior to a high-fat meal effectively reduces postprandial TG concentrations to a similar degree in both NW and OW adolescents, but does not reduce the concomitant postprandial increase in WBC or IL-6.