Abstract： Objective To prepare the Fe3O4 loaded polymer microspheres(Fe3O4/PLGA),and to investigate the influence of Fe3O4/PLGA combined with high-intensity focused ultrasound (HIFU) on rabbits bearing breast tumor.Methods Double emulsion method were utilized to prepare the Fe3O4/PLGA.14 days after implantation of VX2 tumor in breast,32 rabbits were randomly divided into four equal groups.In group Ⅱ,Ⅲ,and Ⅳ,the rabbits received a percutaneous injection of 0.5 ml saline,PLGA,and Fe3O4/PLGA microcapsules solution into breast tumor at 3,6,9,12 dots,about 3 mm around the tumor respectively,and massaged for 1 min before receiving HIFU ablation,while HIFU group received HIFU ablation only.HIFU ablation parameters were the same:"ablated-dot" mode,acoustic power 150 W,exposure duration 5 s.After HIFU ablation,the volume of coagulative necrosis was calculated,HE staining,TEM and immunohistochemical examination of PCNA were performed to detect the structure changes of the targeted tissue caused by HIFU ablation.Results The volume of coagulative necrosis caused by HIFU ablation was substantially larger and the positive index of PCNA was lower in the necrotic region after the injection of Fe3O4/PLGA microcapsules compared to the group without injection agents,the group of saline and the group of pure PLGA microspheres under the same irritation(P ＜0.05).Pathological examination demonstrated the targeted tissue was destroyed severely,Fe3O4 nanoparticles were seen depositing in residual tumor cells under TEM.Conclusions The self-made Fe3O4/PLGA microspheres can effectively enhanced the biomedical effect of HIFU surgery on rabbits bearing VX2 breast tumor.