OBJECTIVE: This study sought to investigate the effectiveness of hepcidin in renal ischemia/reperfusion injury by using a rat model of renal IRI. METHODS: In our study, male Sprague-Dawley rats were divided into a hepcidin-treated group and a control group before establishing the animal models. According to the difference of the modelling methods (renal pedicle occlusion for 45 minutes or not) and renal reperfusion time, the rats were then respectively divided into four subgroups: sham, IRI 4 h, IRI 12 h, and IRI 24 h. After the establishment of the IRI model, the rats were killed to determine renal function, histology, iron metabolism indexes in plasma and tissues, and the expression level of hepcidin and ferroportin-1. RESULTS: <0.05). CONCLUSION: Hepcidin has a reno-protective effect in renal IRI by possibly promoting iron intake in the spleen, inhibiting iron absorption and exportation in the duodenum, alleviating the degree of serum iron, and reducing renal iron accumulation in the renal IRI.