Diabetes mellitus is associated to micro- and macro-vascular lesions responsible for myocardial infarction, nephropathy, retinopathy and polyneuropathy. Four main pathogenic mechanisms have been proposed, all associated with hyperglycaemia: 1) increased flux in the polyol pathway; 2) increased flux in the hexosamine pathway; 3) protein kinase C activation; and 4) increased formation of advanced glycation endproducts. A common mechanism seems to play a central role in the activation of these various pathways. Indeed, an increased production of free radicals by mitochondria induced by hyperglycaemia may be responsible for the observed metabolic disturbances. The present article describes that theory and presents its possible therapeutic implications.