Objective To investigate the injury effect of high intensity focused ultrasound (HIFU) on solid tuberculous rat models..Methods By subcutaneous injection of 1 mL of Mycobacterium smegmatis (MS) suspension in the hip of SD rats, 10 successfully established MS TB infection model of SD rats were divided into HIFU group and control group, each group 5, HIFU treatment group was irradiated for 15 s ( frequency of 1 MHz , sound intensity of 6369 W/cm2) while control group for 15 s ( frequency of 1 MHz , sound intensity of 0 W/cm2).The changes of B-mode ultrasonic grayscale of nodules before and after irradiation were observed in the two groups. HE staining and acid-fast staining were used to observe the pathological changes of nodule tissues under optical microscope.The effects of HIFU irradiation damage were observed by confocal laser and scanning electron microscope.Results There was a statistically significant difference in the B - ultrasound grayscale of the tuberculous nodules in the HIFU group (P=0.004).HE staining: under the optical microscope, the skin tissue structure was intact and the skin attachment structure was normal in the control group. No obvious inflammatory infiltration was found. The structure of the skin tissue was intact under the optical microscope of the HIFU group, no damage was observed to the dermal tissue, and the skin appendages were normal.Inflammatory cells infiltrate and present acute injury. Acid-fast staining: MS in the control group was clustered, while MS in the HIFU group was dispersed and appeared as a short rod. Compared with the control group, the survival rate of MS bacteria in HIFU treatment group decreased from 93.613% to 48.596% significantly. After HIFU irradiation, the surface of MS cell became rough and the cell wall of the cell was broken. Conclusion HIFU at a certain dose (irradiation intensity 6369 W/cm2) can effectively inhibit the infected MS tuberculosis nodules in SD rats, which is expected to be a new method for the treatment of tuberculosis.