Abstract: OBJECTIVE To investigate potential protection and mechanism of fenofibrate on renal ischemia reperfusion injury. METHODS All of 24 male C57BL/6 mice were randomly divided into three groups: Sham group, kidney ischemia reperfusion injury group(IRI group), and fenofibrate pretreatment group(FENO group). The mice in IRI group and Sham group were treated by different methods. Then the pathology of renal tissues was observed according to PAS staining and the protein level of JAK2, STAT3, p-JAK2, p-STAT3 and Caspase 3 were measured by Western blot. RESULTS Compared with the Sham group, the serum levels of Cr and BUN in IRI group were significantly higher. Moreover, renal tubular necrosis, protein tube formation, inflammatory cell infiltration, and the protein expression level of p-JAK2 p-STAT3 were significantly increased as well as the expression of Caspase 3 was significantly reduced, but the protein expression level of JAK2 and STAT3 had no difference. However, compared with the IRI group, the serum levels of Cr and BUN in FENO group were significantly reduced. Moreover, renal tubular necrosis, protein tube formation, inflammatory cell infiltration, and the protein expression level of p-JAK2 , p-STAT3 were decreased as well as the expression of Caspase 3 was significantly increased, but the protein expression level of JAK2 and STAT3 still had no difference. CONCLUSION Fenofibrate pretreatment ameliorates renal ischemia reperfusion injury by reducing apoptosis though inhibiting activating JAK2/STATA3 signal pathway.