Pain is a natural alarm that aids the body in avoiding potential danger and can also present as an important indicator in clinics. Infrared laser-evoked potentials can be used as an objective index to evaluate nociception. In animal studies, a short-pulse laser is crucial because it completes the stimulation before escape behavior. The objective of the present study was to obtain the temporal and spatial temperature distributions in the skin caused by the irradiation of a short-pulse laser. A fast speed infrared camera was used to measure the surface temperature caused by a CO2 laser of different durations (25 and 35 ms) and power. The measured results were subsequently implemented with a three-layer finite element model to predict the subsurface temperature. We found that stratum corneum was crucial in the modeling of fast temperature response, and escape behaviors correlated with predictions of temperature at subsurface. Results indicated that the onset latency and duration of activated nociceptors must be carefully considered when interpreting physiological responses evoked by infrared irradiation.