Anemia is a widespread public health problem. The psychological stress decreases serum iron level and inhibits erythropoiesis. However, the molecular mechanisms involved, leading to iron mal-regulation are not well known. We used a communication box paradigm to induce psychological stress and found that serum iron level decreased after 3 d while liver iron storage increased after 7 d. Moreover, psychological stress up-regulated expressions of interleukin-6 (IL-6) and hepcidin, while down-regulating ferroportin expression after 3 d. These changes were blocked by the injection of IL-6 monoclonal antibody. In conclusion, the IL-6-hepcidin axis is up-regulated by psychological stress in rats, resulting in hypoferremia and increase of hepatic iron storage. (C) 2008 Elsevier Inc. All rights reserved.