The importance of psychological stress is found in the etiology and pathology of more and more diseases. It has been reported that hepcidin is up-regulated by psychological stress, however, TFR2 is a direct regulatory role of the gene on hepcidin expression. Our aim was to evaluate the regulation of TFR2 and the series of molecular mechanisms corresponding to psychological stress. We used a communication box paradigm to induce psychological stress and found that hepatic iron increased as haemosiderin, ferritin and non–transferrin-bound iron induced by quantitative iron analysis and Perl’s staining after 7 d. Psychological stress down-regulated serum transferrin saturation and up-regulated hepatic transferrin receptor 2 after 3 d, then down-regulated hepatic transferrin receptor 1 and up-regulated hepatic ferritin mRNA/protein expression after 7 d. Simultaneously, the levels of hepatic non–transferrin-bound iron, malondialdehyde and superoxide dismutase activity all increased after 7 d. The present study suggested that TFR2 should be another regulator of hepcidin and contribute to hepatic iron accumulation.