Diabetic foot ulcers constitute a major health problem and they are recalcitrant to healing due to a constellation of intrinsic and extrinsic factors. The purpose of this article is to review the potential biological mechanisms that deter healing and perpetuate inflammatory responses in chronic diabetes foot ulcers. The link between hyperglycemia induced oxidative stress and its negative impact on cellular functions are explained. Key evidence related to alteration in tissue perfusion, bacterial balance, sustained proteases and cytokines release, leukocyte function, and growth factor production at the local wound level are summarized. Copyright © 2008 John Wiley & Sons, Ltd.