Objective: Moderate alcohol consumption is associated with a decreased risk of type II diabetes. This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity. Subjects: Twenty healthy, lean (body mass index (BMI) 18.5-25 kg/m2; n=11) or overweight (BMI>27 kg/m2; n=9) men (18-25 years). Methods: Three cans of beer (40g alcohol) or alcohol-free beer daily during 3 weeks. Results: Adiponectin and ghrelin concentrations increased (P<0.01) by 11 and 8%, while acylation-stimulating protein (ASP) concentrations decreased by 12% (P=0.04) after moderate alcohol consumption. Concentrations of leptin and resistin remained unchanged. Insulin sensitivity by an oral glucose tolerance test (OGTT) was not affected by moderate alcohol consumption, but 2h glucose concentrations were lower (P=0.01) after beer (4.5±0.1 mmol/l) than alcohol-free beer (4.9±0.1 mmol/l). Both free fatty acids and glucagon concentrations showed a stronger increase (P<0.01) after 90min during OGTT after beer than alcohol-free beer. Changes of adiponectin were positively correlated (r=0.69, P<0.001), and changes of leptin (r=-0.53, P=0.016) and ASP (r=-0.43, P=0.067) were negatively correlated with changes of insulin sensitivity index. All these results did not differ between lean and overweight men. Conclusions: Moderate alcohol consumption increased adiponectin and ghrelin, while it decreased ASP concentrations both in lean and overweight men. These changes are in line with the hypothesized improvement of insulin sensitivity, but did not affect insulin sensitivity within 3 weeks of moderate alcohol consumption.