People spend most of their time in the non-fasting or postprandial state. Increased sitting time in the postprandial state may amplify the magnitude of elevation in postprandial plasma triglyceride levels, an independent risk factor for cardiovascular diseases. PURPOSE: To determine the extent to which running with extended sitting or walking can attenuate the postprandial plasma triglycerides. METHODS: Eight healthy, young men (23.7 ± 1.5y, VO2max of 50.1±01.7 ml/min/kg) participated in a randomized crossover study with 3 trials. Each trial included a control period (CON, Day 1 and 2), and an intervention day (INTV, Day 3). On the following day (Day 4), plasma triglyceride response was measured hourly over 6 hours after eating a high fat meal containing 1.2 g/kg of fat, 1.1 g/kg of carbohydrate, and 0.22g/kg of protein. During INTV, participants performed either prolonged sitting (SIT), prolonged sitting with 1h of running (RUN; 63.9 ± 2.4%VO2max) or an intermittent walking trial, energetically matched with RUN (WALK; 24.7 ± 2.3%VO2max). Daily step number and body position were monitored and caloric intake and macronutrient content were controlled for all trials. RESULTS: Sitting time was 408 ± 39, 361 ± 23 min and 226 ±19 min for SIT, RUN and WALK (all p<0.05) over the 9-hour intervention period on Day 3. Daily step numbers on Day 3 were 11850 ± 198, 25426 ± 1367, and 1571 ± 97 for RUN, WALK, and SIT (all p<0.001). There were no differences in exercise energy expenditure (RUN, 600± 36 kcal vs. WALK, 607± 33 kcal). RUN significantly reduced the incremental area under the curves for plasma triglycerides, compared to WALK (18%; p<0.05) and SIT (40%; p<0.05). Furthermore, the incremental area under the curves for plasma triglycerides was 18% lower (p<0.05) in WALK, compared to SIT. CONCLUSIONS: Despite a prolonged period of sitting, moderate intensity running is more effective in lowering postprandial elevation of plasma triglycerides, compared to energy matched low intensity walking. However, both running and walking are effective in reducing postprandial triglycerides, compared to sitting alone.