BACKGROUND Adipose tissue-derived hormones act as key mediators that may link active lifestyles to improved cardiovascular function. This study tested the hypothesis that a single weight training session would beneficially modulate adipokine profile in a way that would exert protection against endothelial dysfunction, in trained but not sedentary subjects. METHODS Male subjects (n = 43) were categorized into four separate groups based on exercise history: 1) sedentary, 2) weight trainers, 3) runners, or 4) weight trainer + runners. All subjects underwent a single progressive leg press weight training session (low weight for two sets of 8-12 repetitions each and then near-maximal exertion for three sets of 8-12 repetitions each). RESULTS There were no differences between groups for age, body weight, BMI, waist circumference, or percent body fat. Adiponectin increased (P < 0.05) by 30% and 37%, whereas resistin decreased (P < 0.05) by 35% and 34% in the weight trainers and weight trainer + runners, respectively, after training. Flow-mediated dilation (FMD) was impaired (P < 0.05) in sedentary subjects (-1.1 +/- 0.3%) but not in the athletic groups (1.7 +/- 0.4%). Improvements in FMD were associated with increased adiponectin (r = 0.61, P = 0.01), and decreased resistin (r = -0.56, P = 0.01) in weight trainers only. Leptin was not altered by acute resistance training in any group. There were no differences after training for total, LDL, HDL cholesterol, triglycerides, C-reactive protein levels, and systolic or diastolic blood pressure. Increased adiponectin was related to higher levels of HDL cholesterol after intervention (r = 0.71, P = 0.001). CONCLUSIONS These findings suggest that habitual resistance training may modulate adipokine profiles in a way that is protective against endothelial dysfunction.