Background: On one side, single bouts of muscle damaging eccentric exercise (EE) affect glucose metabolism negatively while single bouts of concentric (CE) have positive acute short-term effects on glucose metabolism. On the other side, it has been proposed that long-term endurance EE might be more effective in improving glucose metabolism than long-term CE when adjusted for energy expenditure. This would imply that adaptations of glucose metabolism are dependent on the type of exercise. However, acute effects of not muscle damaging EE are not known. Interleukin-6 (IL-6) released from the exercising muscles may be involved in and could therefore explain acute adaptations on glucose metabolism. The aim of Study A was to assess the effects of a single bout of CE and a single bout of not muscle damaging EE on glucose metabolism and IL-6 secretion. The aim of Study B was to investigate the effects of a single bout of CE and a single bout of EE inducing no muscle damage and matched for energy expenditure, on glucose metabolism. Methods: (Study A) Seven sedentary non-smoking, healthy males (age: 27.4 5.1 years; BMI: 22.5 1.7 kg · m-2; VO2peak: 49.3 4.2 ml · kg-1 · min-1) participated in a crossover trial. (Study B) Seven healthy but sedentary female participants (age: 20.7 2.9 years; BMI: 20.6 2.6 kg · m-2; VO2peak: 39.0 4.5 ml · kg-1 · min-1) took part in a randomized cross over trial. Both trials consisted of 1 hour uphill (CE) respectively downhill (EE) walking on a treadmill. Venous blood samples were drawn before, directly after and 24h after exercise. An oral glucose tolerance test (OGTT) was performed before and 24h after exercise. Results: (Study A) Glucose tolerance (1 hour and 2 hours values of the OGTT) significantly improved 24 hours after CE (-10.12 3.22 %: p = 0.039; -13.40 8.24 %: p = 0.028). After EE only the 1 hour value of the OGTT was improved (-5.03 5.48 %: p = 0.043). Acute IL-6 concentration rose significantly after CE but not after EE. (Study B) CE and EE lead to comparable changes of glucose tolerance (area under the curve of the OGTT) (-16.0 25.81 mg · dl-1 · h-1 vs. -6.3 45.26 mg · dl-1 · h-1, p = 1.000) and HOMA insulin resistance (-0.16 1.53 vs. -0.08 0.75, p = 0.753). Compared to baseline, IL-6 concentration increased significantly immediately after EE (1.07 0.67 vs. 1.32 0.60 pg · ml-1, p = 0.028) and tended to increase immediately after CE (0.75 0.29 vs. 1.03 0.21 pg · ml-1, p = 0.058). Compared to baseline, TNF- concentration decreased significantly immediately after EE (1.47 0.19 vs. 1.06 0.29 pg · ml-1, p = 0.046) but not after CE (1.27 0.43 vs. 1.24 0.43 pg · ml-1, p = 0.686). Conclusions: We conclude that both a single bout of CE and a single bout of not muscle damaging EE elicit positive changes in glucose tolerance even in young and healthy subjects. Acute effects of a single bout of exercise, inducing no or just mild muscle damage, on glucose tolerance and insulin resistance seem to be primarily energy expenditure dependent whereas acute anti-inflammatory activity induced by a single bout of exercise appears to be rather exercise type dependent.