Vascular responses were monitored to understand the role of the microvasculature in tumor destruction as a result of photodynamic therapy (PDT). Rats received an intravenous dose of 2 mg/kg Benzoporphyrin Derivative (BPD), at 20 min, 4 h, or 7 h before laser irradiation. With Photofrin (10 mg/kg), drug-light intervals were 20 min or 8 h. Jejunal blood vessels were exposed to 12 J/cm2 at 690 nm (with BPD) or at 630 nm (with Photofrin). Optical Doppler tomography (ODT) was used to evaluate PDT-induced changes in vessel diameter and blood flow. At the shortest drug-light time interval (20 min), BPD-mediated PDT caused transient constriction of arteries, accompanied by decreased blood flow, followed by vasodilation until baseline was reached or overshoot occurred. Veins became occluded with no restoration of the vessel lumen. At longer drug-light intervals, vasoconstriction diminished and venodilation was observed. With Photofrin, vasoconstriction and venodilation increased with the drug-light interval. Application of a higher light dose (48 J/cm2) resulted in irreversible hemostasis. ODT can be used to study changes in lumen diameter and blood flow, which are important diagnostic parameters of PDT.