We report on development of an optical-thermal model to evaluate the use of pulsed photothermal radiometry (PPTR) for depth profiling of port wine stain (PWS) skin. In the model, digitized histology sections of a PWS biopsy were used as the input skin geometry. Laser induced temperature profiles were reconstructed from simulated PPTR signals by applying an iterative, non-negatively constrained conjugate gradient algorithm. Accuracy of the following PWS skin characteristics extracted from the reconstructed profiles was determined: (1) average epidermal thickness (2) maximum epidermal temperature rise (3) depth of PWS upper boundary and (4) depth of maximum PWS temperature rise Comparison of the actual and reconstructed profiles from PPTR data revealed a good match for all four PWS skin characteristics. Results of this study indicate that PPTR is a viable approach for depth profiling of PWS skin. © 2004 Society of Photo-Optical Instrumentation Engineers.