Transient receptor potential melastatin 8 (TRPM8) is a member of the melastatin subfamily of TRP channels which are permeable to cations such as Ca2+ and Na+.TRPM8 is widely expressed in various tissues including neurons, lungs, prostate, bladder and blood vessels.The most important physiological function of TRPM8 discovered so far is its role in sensory neurons as the temperature sensor.TRPM8 channels can be activated by cold temperature and cooling agents such as menthol and icilin.In addition to these, very few chemical activators have been identified yet.In this study we found that borneol activated TRPM8 channels exogenously expressed in HEK293 cells in both intracellular Ca2+-imaging and electrophysiological experiments.The potency of borneol is lower than that of menthol at same concentration.The action site of borneol is located within the intracellular domains of TRPM8 channels, as revealed by inside-out patch recordings.We also found that bomeol significantly reduced the tension of rat mesenteric arteries stimulated by high K+ or phenylephrine, and detected TRPM8 expression in these vessels by RT-PCR.These results suggest that activation of TRPM8 channels by borneol may contribute to its vasodilatory effect, which is supportive of the proposition that TRPM8 plays a role in the regulation of vascular tone.