Pulsed water jet is an emerging surgical instrumentation intended to achieve both maximal lesion resection and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The piezoelectric actuator-driven pulsed water jet (ADPJ) is a new technology that can deliver a precisely controlled uniform and efficient pulsed water jet with minimum water flow. The present study evaluated the ADPJ system in preclinical animal studies in the swine brain, and investigated breaking strength, one of the parameters for mechanical properties, to elucidate the mechanism of tissue selectivity for tissue dissection by the water jet. This system consisted of a pump chamber driven by a piezoelectric actuator, a stainless steel tube, and a nozzle (internal diameter: 0.15 mm). Water was supplied at 6 ml/min. The relationship between input voltage (3-25 V at 400 Hz) and peak pressure was measured using a pressure sensor through a sensing hole. The temporal profile of dissection depth during moving application was evaluated using gelatin brain phantom and swine brain. The dissected specimens were evaluated histologically. The mechanical property (breaking strength) of the swine brain was measured by a compact table-top universal tester. Peak pressure increased linearly with increase in input voltage, which reflected the dissection depth in both the gelatin brain phantom and swine brain. Small arteries were preserved, and minimum damage to surrounding tissues occurred. The breaking strength of the arachnoid membrane (0.12 ± 0.014 MPa) was significantly higher compared with the gray matter (0.030 ± 0.010 MPa) and white matter (0.056 ± 0.009 MPa; p < 0.05). The breaking strength of the gray matter corresponded to that of 3 wt% gelatin, and that of white matter corresponded to a value between 3.5 and 4 wt% gelatin, and the dissection depth seemed to be estimated at 3 to 4 wt% gelatin. The present study suggests that the ADPJ system has the potential to achieve accurate tissue dissection with preservation of blood vessels in neurosurgery. The difference in breaking strength may explain the tissue selectivity between the brain parenchyma and tissue protected by the arachnoid membrane.