BACKGROUND: In animal experiments, ultrasound-mediated microbubbles can promote the homing of transplanted stem cells to the ischemic area, enhance angiogenesis and small arterial formation, improve local blood flow in the ischemic myocardium and restore myocardial contractility.OBJECTIVE: To investigate the effect of ultrasound-mediated microbubbles on intravenously transplanted bone marrow mesenchymal stem cell (BMSC) homing and the therapeutic efficiency on ischemic stroke. METHODS: A middle cerebral artery occlusion (MCAO) model was induced by plug wire preparation. At 72 hours after MCAO, model rats were randomized into four groups: PBS group (n=15), BMSCs group (n=18), ultrasound+BMSCs group (n=18), ultrasound+microbubble+BMSCs group (n=18). Corresponding treatment was done in each group: 2 mL of PBS was injected via tail vein in the PBS group; about 3×106 BMSCs diluted by 2 mL of PBS were injected via tail vein slowly in the BMSCs group; after skull ultrasound radiation (1 MHz, 2 W/cm2) for 120 seconds, BMSCs were injected via tail vein slowly in the ultrasound+BMSCs group; the same process as the ultrasound+BMSCs group was done following intravenous injection of 0.1 mL/kg microbubbles in the ultrasound+microbubble+BMSCs group.RESULTS AND CONCLUSION: (1) Forty-eight hours after BMSCs transplantation, the BMSCs homing rate in the brain was significantly higher in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (2) Twenty-eight days after MCAO, nerve damage was significantly milder in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (3) Seven days after transplantation, the water content in the brain tissue was significantly lower in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (4) Seven days after transplantation, the cerebral infarction volume was significantly reduced in the ultrasound+microbubble+BMSCs group compared with the other two groups (P < 0.05). To conclude, ultrasound-mediated microbubbles can enhance the homing effect of intravenously transplanted BMSCs, reduce cerebral edema and cerebral infarction volume, improve the neurological function, and increase the therapeutic effect of BMSCs transplantation on ischemic stroke.