Objective We established the animal models of obesity induced by high-fat diet, in order to study the mRNA and protein expression of regulation molecules related with iron metabolism about hepcidin, lipocalin-2 (LCN2), ferroportin-1 (FPN1) in obese mice's liver and the molecular regulation mechanism. Methods C57BL/6J (4～6 weeks) mice were randomly divided into control group and obesity model group, each group of ten. The obesity group were fed with a high-fat diet and the control group were given the normal diet for lasting 15 weeks. After we successfully established the obesity animal model, the expression level of hepcidin, LCN2 and FPN1 mRNA in the liver were measured by Real-time fluorescent quantitative PCR method and the protein expression level of LCN2 and FPN1 were measured by Western-Blot. Results Compared with the control group, the expression level of hepcidin mRNA in the liver was increased in obesity group (P < 0.05), however, the expression level of LCN2, FPN1 was no significant difference (P > 0.05). Conclusion Obesity can increase the expression of hepcidin mRNA, however, there was no significantly effect on the expression of LCN2, FPN1. So, we can't think that obesity can affect the expression of LCN2 and FPN1, lead to the ability of cells uptake and release iron abnormal, then appear iron metabolism disorders. As a result, leading to iron deficiency. Maybe obesity can affect other regulatory molecules related with iron metabolism through up-regulation the expression of Hepcidin or the more complex regulatory mechanisms. We still need further experimental research and exploration. This research also provides the basis of theoretical and experimental for the further study the effects of obesity on the expression of regulation molecules related with iron metabolism in obesity mice's liver and the mechanism of iron deficiency.