Although studies have shown that photothermal therapy can coagulate selectively abnormal vasculature, the ability of this method to achieve consistent, complete removal of the vasculature is questionable. We present the use of multimodal, wide-field functional imaging to study, in greater detail, the biological response to selective laser injury. Specifically, a single-platform instrument capable of coregistered fluorescence imaging and laser speckle imaging was utilized to monitor vascular endothelial growth factor gene expression and blood flow, respectively, in a transgenic rodent model. Collectively, the longitudinal, in vivo data collected with our instrument suggest that the biological response to selective laser injury involves early-stage redistribution of blood flow, followed by increased vascular endothelial growth factor promoter activity to stimulate pro-angiogenic events.