Abstract:[Objective] To explore the effect on mechanism of irisin combined with extracorporeal shock wave (ESW) on fracture heal- ing in the ovariectomized rats. [Methods] A total of 80 SD rats were randomly divided into 5 groups with 16 rats in each group, including sham operation group, model group, model +ESW group, model + irisin group, model +ESW+ irisin group. Except the animals in sham oper- ation group that received surgical incision only, all rates received bilateral ovariectomy, and then left femoral fracture and internal fixation successively, subsequently, corresponding postoperative treatments were given respectively, including ESW treatment once a week, and lo- cal injection of irisin group in fracture site. At 4 weeks after treatment, the animals were sacrificed for bone mineral density, osteoclast in- dex, microCT, Western blot and RT-QPCR assays. [Results] Bone mineral density and osteoclast index were ranked superior-inferiorly in orders of sham operation group > model + ESW + irisin group > model + ESW group or model + irisin group > model group (P>0.05) . Mi- croCT detection items, including BS/BV, Tb.N, Tb.Th and Tb also ranked superior-inferiorly in sequence of model + ESW+ irisin group > model +ESW group or model + irisin group > model group (P<0.05) . In term of Western blot detection, the relative protein expression of BMP2, VEGF, Nrf2F and OH-1 arranged up-down in order of sham operation group > model + ESW+ irisin group > model +ESW group or model + irisin group > model group (P<0.05) . In term of RT-QPCR assay, the relative mRNA expression of Nrf2 and OH-1 from high to low were: sham operation group > model +ESW+ irisin group > model + irisin group or model +ESW group > model group (P<0.05) . [Conclusion] Irisin combined with ESW might activate Nrf2/OH-1 pathway to promote the expression of VEGF and BMP2 proteins, and pro- mote fracture healing in the ovariectomized rats