A considerable part of the World's population: 135 million in 1995, predicted to be 300 million in 2025, suers from Diabetes Mellitus. Unfortunately, many people still die as a direct consequence of this disease or pathologies associated with it (neuropathy, retinopathy, nephropathy and arterial disease). Diabetes Mellitus is a condition characterized by abnormal glucose tolerance with a tendency to hyperglycaemia and is due to a relative or absolute de®ciency of Insulin. Two types of Diabetes Mellitus have been identi®ed so far: (a) Type I or Insulin Dependent Diabetes Mellitus typically aects younger people and has an acute onset; patients do not produce the hormone insulin and the treatment is the administration of daily injections of the hormone (b) Type II or Non-Insulin Dependent Diabetes Mellitus typically aects middle-aged, elderly and obese people and has a more gradual onset; patients produce the hormone but the body is not able to use it. The treatment for Type II patients involves administration of oral hypoglycaemic drugs, but after several years some patients require the administration of insulin. Insulin is an hormone produced by the pancreas (b-cells) which is essential for fat and carbohydrate metabolism and although much eort has been expended in this ®eld of research, the mechanism of insulin action is still not well understood. Since the late 1970's the element vanadium has been associated with insulin and its role in the body [1]. Control of glucose levels in the blood plasma has been achieved in vitro and in vivo by oral administration of vanadium in the form of inorganic salts [2±5]. As a drawback, it has been shown that the element is poorly absorbed in its inorganic forms and the required high doses have been associated with undesirable side eects. The possibility of using synthetic vanadium compounds that can be administered orally and can produce insulin-like eects is of course very exciting, and the search for compounds that may carry vanadium in a form that can be better absorbed has been an intense ®eld of research. Studies on vanadyl complexes of the VO(N2O2) type [6±9], VO(N3O2) [10], VO(N2O3) [11], VO(S2O2) [12], VO(S2N2) [13], VO(S4) [14, 15] and VO(O4) [16±19] has proved that these complexes exhibit insulin-mimetic behaviour and are eective in smaller amounts [20±23]. In vivo studies revealed that the serum levels of glucose (G) and free fatty acids (FFA) correlate well in both normal and STZ-rats and that the FFA serum level is also a good index for assessing the degree of Diabetes Mellitus [24, 25]. Both serum glucose and FFA levels in STZ-rats are normalized by vanadyl treatment and in vitro studies in adipocytes suggested that normalization of the FFA levels in serum is due to the inhibition of FFA release induced by vanadyl compounds [25]. With the objective of providing a new family of insulin-mimetic complexes with a VO(O4) coordination mode, we synthesized and characterized several 1,2substituted-3-hydroxy-4-pyridinone oxovanadium(IV) complexes [26]. The idea of preparing oxovanadium(IV) pyridinone complexes arose as a consequence of work developed on the structure and solvation of a variety of pyridinone complexes of other metals [27±29] namely, aluminium and iron, and was based on the knowledge that pyridinones have proved to be more eective in the treatment of b-thalassemia than pyrones [30±33]. Pyridinone ligands (Figure 1), that can be synthesized by reaction of pyrones (Figure 1) with primary amines, are better chelators and are particularly attractive for pharmaceutical purposes, since their structure allows tailoring of their hydrophilic/lipophilic balance (HLB) [30±33] without signi®cantly changing its chelating properties. Such a possibility is of paramount importance for the compounds to be used in vivo, as the HLB is a crucial parameter for the transport properties of the ligands and complexes across biomembranes. The pharmaceutical importance of pyridinones has already been recognized, in iron and aluminium chelation therapy and in the administration of gallium and indium isotopes in radiodiagnosis and radiotherapy [34±36]. In this work we describe the research that is being developed on the vanadium pyridinone compounds including both its chemistry and the insulin-like tests performed in vitro.