Objective To evaluate the usefulness of pulsed infrared solid-state Holmium: Yttrium-Aluminum-Garnet (Ho:YAG) laser in neurosurgery, acute responses of brain tissue to Ho:YAG irradiation and to investigate the healing processes in rats and rabbits. Methods Animals were divided into groups according to different survival time and laser irradiation mode. Craniotomy was made and laser energy was delivered to the brain surface by two irradiation modes: 1) contact mode with the fiber in contact with the brain surface; and 2) non-contact mode with the fiber tip 5 mm above the brain surface. Gross observations were made and histological changes were studied. Results Acute responses were studied on rats' brain. The contact mode produced a crater lined with less than 1 mm thick thermally coagulated layer of brain tissue. The non-contact mode effectively vaporized the brain tissue even with water irrigation. Good homeostatic effect was achieved. The shock waves generated by the pulsed delivery of laser energy, however, impacted on the brain resulting in debris spreading and brain vibration. The healing processes were studied on rabbits' brain one day to six weeks after irradiation. The lesions produced by the contact mode were narrow and sharply defined. With the non-contact mode, the thickness of the coagulated layer at the bottom of the crater varied between 0.8 and 1.1 mm.Conclusions Ho:YAG laser should be a clinically useful tool in neurosurgery because of its good ablation effect, shallow penetration and convenient optic fiber transmission system. Meanwhile, a continuously waved Ho:YAG laser is desired to reduce the shock wave impact.