Fetuin-A, particularly the phosphorylated isoform, appears to attenuate insulin action by suppressing insulin receptor tyrosine kinase activity. In fact, fetuin-A is elevated in obesity, insulin resistance and Type 2 diabetes. Aerobic exercise is known to improve insulin action; however, the fetuin-A response to exercise in men with metabolic syndrome is unknown. PURPOSE: Our purpose was to characterize the influence of a single episode of aerobic exercise on fetuin-A and markers of insulin action in obese men with metabolic syndrome. METHODS: Ten men (39 + 8 yrs of age; BMI = 35.6 + 6.7 kg·m²; % fat = 38 + 5; VO2max = 28.8 + 6.2 mL·min^-1·kg^-1; waist circumference = 45.9 + 6.3 in; HDL-C = 36 + 6 and triglycerides = 163 + 99 mg/dL; HOMA score = 5.3 + 4.4) expended 500 kcals by treadmill walking at 60-70% of VO2max. Fasting blood samples were collected prior to, immediately, and 24 hr post-exercise. Samples collected during a 2 hr oral glucose tolerance test (OGTT, 75g glucose load) were obtained prior to and 24 hr after exercise. Changes in serum glucose, insulin, non-esterified fatty acids, fetuin-A, phosphofetuin-A concentrations, HOMA, the glucose/insulin ratio, and OGTT areas under the curve (AUC) for glucose, insulin, fetuin-A and phosphofetuin-A were determined by multiple repeated-measures ANOVAs. RESULTS: The glucose/insulin ratio increased 92% 24 hr after exercise (p = 0.0067) and the insulin AUC was reduced 16% post-exercise (p = 0.049). Serum phosphofetuin-A AUC was significantly lower (p<0.006) 24 hours after a single bout of exercise. HOMA (p = 0.062) and fetuin-A concentrations remained unchanged with exercise. CONCLUSIONS: The reduced phosphofetuin-A AUC observed after a single exercise session is consistent with improvements in surrogate markers of insulin sensitivity and may be a mechanism by which exercise improves insulin action.