We pathologically investigated the effects of water irrigation during Er:YAG laser irradiation on wound healing in mouse skin. Fifty-one 6-week-old ICR male mice were used in the present study. Dermal wounds were generated on the skin of the backs using the Er:YAG laser at 100 mJ/pulse and 10 Hz with (4 ml/min) or without (control) water irrigation. Mice were then sacrificed on 0, 1, and 3 days after laser irradiation, and the crust of the skin and thickness of the thermal coagulation layer were evaluated pathologically. The epidermis extended faster in the water irrigation group than in the control group on 1 day. The epidermis with keratinized layers became thicker and the crust had completely detached after 3 days in the water irrigation group. The thermal coagulation layer was thinner in the water irrigation group than in the control group. Apoptotic cell death was prominent in the control group. Detachment of the crust was observed after 3 days in 50% of the water irrigation group and 20% of the control group. These results demonstrated that Er:YAG laser irradiation with water irrigation promoted faster wound healing