Abstract：Diabetic ulcer is the most important factor leading to clinical amputation. In the present study, 1H NMR-based metabonomics combined with pathological and biochemical analysis were used to study the metabolic characteristics and pathological mechanisms of diabetic ulcers. The results showed that the fibroblast and blood capillaries proliferation in skin ulcers of diabetic rats were significantly weaker than those in the control rats. From the scores plots of metabonomic studies, we found distinct, easily detectable differences between (a) diabetic ulcer rats and control rats, and (b) diabetic ulcer rats with different healing time. Compared to control skin ulcers, diabetic skin ulcers had lower levels of leucine, isoleucine, alanine, citrate, choline and betaine, together with higher levels of lactate, acetate, pyruvate, creatine, taurine and glycine. Altered metabolite concentrations are most likely the result of the cells switching to glycolysis and creatine metabolism to maintain energy homeostasis following the loss of ATP caused by impaired TCA cycle in diabetic ulcers and to repair the skin trauma. The present study may be able to assist deeply understanding of diabetic ulcers and selection of treatment protocols.