Biological effects in the microwave band of the radiofrequency (RF) spectrum are thermally mediated. For acute high-power microwave exposures, these effects will depend on transient time-temperature histories within the tissue. In this article, we summarize the transient temperature response of rats exposed to RF energy emanating from an open-ended rectangular waveguide. These exposures produced specific absorption rates of approximately 36 and 203 W/kg in the whole body and brain, respectively. We then use the experimentally measured thermal data to infer the baseline perfusion rate in the brain and modify a custom thermal modeling tool based upon these findings. Finally, we compare multi-physics simulations of rat brain temperature against empirical measurements in both live and euthanized subjects and find close agreement between model and experimentation. This research revealed that baseline brain perfusion rates in rat subjects could be larger than previously assumed in the RF thermal modeling literature, and plays a significant role in the transient thermal response to high-power microwave exposures. © 2021 Bioelectromagnetics Society.