Abstract: To evaluate the thermal safety of transcranial photobiomodulation, this study investigates the effects of 808 nm laser irradiation on scalp and mandibular temperatures, as well as safety parameters, when applied to the heads of live mice under varying illumination durations and power levels. Additionally, to evaluate whether a water-cooling device can effectively reduce irradiation-induced temperature increases. The 808 nm laser was directed at the fontanelle of mice. Scalp temperatures were measured using an infrared thermal imager, and jaw temperatures were recorded using a thermocouple. C57BL/6J mice were divided into three groups: Group A (natural cooling), Group B (active cooling), and Group C (negative control). Group A was further subdivided into A1, A2, and A3 based on different power levels of irradiation. Changes in scalp and mandibular temperatures were recorded at an irradiation dose of～140 J. Scalp temperature increased by 4.2℃ in Group A and by 2.4℃ in Group B, with Group B showing a temperature reduction of 1.8℃ compared to the corresponding power level in Group A . Jaw temperature measurements indicated a rise of 3.0℃ in Group A and 2.4℃ in Group B. As the average power of the 808 nm laser increased, local temperatures rose significantly. An average irradiation power of approximately 300 mW and a dose of ～140 J were found to be safe for mouse transcranial irradiation. For higher power levels, active cooling effectively mitigated local temperature increases. The results of this study can provide experimental basis for setting the parameter range of transcranial irradiation in mice.