Visceral adipose tissue (VAT) is detrimental to health, but physical activity can reduce VAT mass. During exercise, skeletal muscle releases IL-6, and IL-6 has been shown to stimulate lipolysis. A new randomized controlled trial investigated changes in VAT mass in 83 adults with abdominal obesity, allocated to receive the IL-6 receptor antibody tocilizumab or placebo during a 12-week intervention of bicycle exercise or no exercise. In participants receiving placebo, exercise reduced VAT mass (−225.1 g, 95% CI −446.7 g to −3.4 g; P = 0.047). By contrast, in participants performing exercise, VAT mass was increased in the tocilizumab group compared with the placebo group (278.2 g, 95% CI 61.69–494.73 g; P = 0.013), indicating that IL-6 is required for VAT mass reduction through exercise.