Vascularization of developing growth plates is integral to the process of endochondral ossification. We hypothesized photodynamic therapy could be used to initiate premature vascularization and calcification of growth plates in mice on the induction of vascular endothelial growth factor. Three-week-old transgenic mice that emit bioluminescence on activation of the vascular endothelial growth factor gene were treated with different regimens of benzoporphyrin derivative mono-acid-mediated photodynamic therapy in the right, proximal tibial growth plate. We quantified changes in vascular endothelial growth factor-related bioluminescence at times after photodynamic therapy in vivo. The expression of vascular endothelial growth factor protein and CD31-labeled vasculature in growth plates also were examined with growth plate histology. Measurements of limb length were assessed in vivo using conventional radiography and confirmed on harvesting. Mice exposed to repeat treatments of 10 J x2 displayed enhanced bioluminescence 2 weeks after photodynamic therapy. Histology confirmed increased vasculature immediately adjacent to the growth plates with evidence of physeal closure. At 4 weeks posttreatment, limbs were shortened by an average of 9.5% +/- 4.4% without complication, confirming the potential application of photodynamic therapy for physiodesis.