Foot ulceration is a debilitating comorbidity of diabetes that may result in loss of mobility and amputation. Optical detection of cutaneous tissue changes due to inflammation and necrosis at the preulcer site could constitute a preventative strategy. A commercial hyperspectral oximetry system was used to measure tissue oxygenation on the feet of diabetic patients. A previously developed predictive index was used to differentiate preulcer tissue from surrounding healthy tissue with a sensitivity of 92% and specificity of 80%. To improve prediction accuracy, an optical skin model was developed treating skin as a two-layer medium and explicitly accounting for (i) melanin content and thickness of the epidermis, (ii) blood content and hemoglobin saturation of the dermis, and (iii) tissue scattering in both layers. Using this forward model, an iterative inverse method was used to determine the skin properties from hyperspectral images of preulcerative areas. The use of this information in lowering the false positive rate was discussed.© (2010) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.