Chronic low-grade inflammation is involved in the development of metabolic disorders including atherosclerosis, Type 2 diabetes (T2D) and metabolic syndrome. Aerobic exercise has been shown to be anti-inflammatory and attenuate postprandial blood lipids, however the effect of exercise on postprandial inflammation remains unclear. The aim of this study was to determine the protective effect of a single bout of aerobic exercise against postprandial lipemia and peripheral blood mononuclear cell (PBMC) inflammation and to evaluate associations with changes in the energy-sensing enzyme, AMP-activated protein kinase (AMPK). Healthy male subjects (n=12, age=23±2, %Fat=19±2) reported to the laboratory following an overnight fast (12-14h) on two separate occasions for consumption of a high-fat meal (HFM). Participants completed an acute bout of aerobic exercise the afternoon prior to one of the HFM visits. Results indicate that the single bout of moderate aerobic exercise increased AMPK activation in PBMCs as shown by increased p-ACC. This may be due to decreases in the AMPK inhibitory kinases PKD and GSK3β. Additionally, prior moderate intensity exercise decreased postprandial lipemia (PPL) and some mediators of the inflammatory pathway, such as NF-κB.