INTRODUCTION: Chronic hypertryglyceridemia is thought to be atherogenic and is associated with an elevated thrombotic potential. Aerobic exercise training is known to reduce plasma triglyceride (TG) levels and the purpose of this study was to determine the effect of a single, high-fat meal on markers of inflammation, coagulation, and fibrinolysis before and after exercise training. MATERIALS and METHODS: Eight subjects were tested for aerobic capacity, body composition, and postprandial lipemia (PPL), followed by 6-months of exercise training and final testing. Blood samples were obtained every 30-minutes following the lipemic challenge for measurement of free fatty acid (FFA), TG, insulin (Ins), and glucose (Glu). Hemostatic variables including factor VII activity (FVIIa), tissue factor pathway inhibitor-factor Xa complex (TFPI/Xa), and plasminogen activator inhibitor-1 (PAI-1) antigen / activity were assessed at 0, 2, and 4 hours postprandial, as well as leukocyte interleukin-6 (IL-6), tumor necrosis factor-&#945; (TNF-&#945;), and PAI-1 gene expression among 4 subjects during the lipemic challenge. RESULTS: The exercise training was of sufficient intensity to increase aerobic capacity (p < 0.0001) and improve body composition (p = 0.04). There were no differences between tests among PPL responses of FFA, TG, Ins, or Glu, however the main effect mean TG response averaged across all time-points was lower at final testing (139 ± 19 mgdl-1) versus baseline (154 ± 24 mgdl-1) (p = 0.02). Furthermore, the 4-hour averages for total fat oxidation rate increased by 68% (p = 0.01) and total carbohydrate oxidation rate decreased by 29% (p = 0.009) from baseline to final testing. IL-6 and PAI-1 gene expression were undetectable in the Paxgene® blood samples, however PAI-1 antigen / activity, FVIIa, TFPI/Xa, and TNF-&#945; gene expression were all improved following exercise training after adjusting for confounders. CONCLUSION: Aerobic exercise training reduces the potential for coagulation, improves fibrinolytic potential, and reduces leukocyte TNF-&#945; gene expression following the ingestion of a high fat meal.