The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9±1.4; age 35±12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9±2.7; age 47.1±11.86) were tested in a resting and a physical activity condition. Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/l×min) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=0.05) as well as in the obese subjects after weight loss (P<0.05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity to acute stimulation.