Foot ulceration is a major complication of diabetes and consumes a major portion of the resources for the treatment of diabetes. Mechanical factors such as high plantar pressures and hallux rigidus are now recognized as important in the understanding and treatment of diabetic foot ulceration. The goal of this study is to investigate the influence of diabetes on the mechanical properties of plantar skin and the skin/fat interface. Four different techniques that covered the spectrum from gross tissue behavior to localized skin imaging were used to investigate tissue properties in diabetic skin. The results demonstrated:​ 1) the strength of skin-fat interface (assessed with a skin-peeling test show) is stronger in both forefoot and heel regions than the mid arch region, and the strength is 27.6% higher in diabetic specimens than in non-diabetic controls, 2) skin specimens from the diabetic group are 12.9% stiffer and less extensible compared with non-diabetic group, 3) fluorescence measurements had peak values and spectral area significantly higher in diabetic skin group than non-diabetic skin group (71% and 72%, respectively), and 4) digital volumetric imaging revealed that the density of dermis of diabetic specimens is 17.4% higher than that of non-diabetic skin specimen. In conclusion, these four tests demonstrate that diabetic skin is not only stiffer, more dense and thicker than control specimens, but these changes are also associated with a skin-subdermal interface that is more resistant to peeling. Together, these results indicate a soft-tissue equivalent to W olffs Law for bone;​ i.e., when diabetic patients subject their skin to elevated pressures, there are mechanical and physiological adaptations that result in specific skin responses. These results suggest that through appropriate biomechanical measurements, the loading history over a long duration for a particular patient can be quantified.