Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.