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Hollow microcapsules have been considered for potential application as drug or gene carriers. Targeted drug or gene release to tumor vascular can be achieved by destroying the capsules by high-intensity ultrasound. This report investigates fabrication of microcapsules having biocompatible polylactic acid (PLA) shell and the mechanical property for the destruction under ultrasound irradiation. The PLA hollow microcapsules with the diameter of 1 to 35 μm were fabricated by double emulsion method. Red fluorescent dye which is substitute for drug was enclosed into the capsules. The capsules have trilaminar structure. Inner air is surrounded by red fluorescent, and the PLA shell encloses them. Shell thickness of capsules was distributed from 100 nm to 3 μm. Destruction of the fabricated capsules was investigated by using ultrasound pulse with the center frequencies from 500 kHz to 2 MHz. The behavior of capsule was observed by using an optical microscope under ultrasound irradiation. The frequency dependence of the capsule destruction was investigated and 35% of the capsules with the resonance size was destroyed with 400 kPa at 700 kHz. The capsule shell was ruptured by the ultrasound, and then the inner dye was released; the dye was completely released for 120 seconds under ultrasound irradiation.