Purpose: To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest. Methods: Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fiber) in a continuous (CONTINUOUS; n=10; 24 h.day-1 at a constant rate) or intermittent (INTERMITTENT; n=10; as 4 meals per day separated by 5 hours) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations. Results: During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42±0.38 vs 0.95±0.48 nmol.L-1, respectively; P=0.014) as were insulin concentrations (interaction effect, P<0.001) which reached a peak of 369±225 pmol.L-1 in CONTINUOUS, compared to 94±38 pmol.L-1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r=0.44, P=0.049). Conclusion: Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may therefore be preferable to continuous provision of nutrition.