Creatine supplementation may exert beneficial effects on muscle performance and facilitate peripheral glucose disposal in both rats and human subjects. The present study was undertaken to explore the effects of creatine supplementation on the ATP, creatine, phosphocreatine and glycogen content of white and red gastrocnemius and soleus muscles and on blood D-glucose and plasma insulin concentrations before and during an intravenous glucose tolerance test in Goto-Kakizaki rats, a current animal model of inherited Type-2 diabetes mellitus. Male 6-week and 14-week old Goto-Kakizaki rats were allowed, for 8 weeks, free access to a normal diet enriched, when so required, with 2% (w/w) creatine monohydrate. Creatine supplementation increased muscle creatine content, especially in the soleus muscle of young rats (+35.5 ± 15.8%; d.f. = 10; p < 0.05), whilst failing to affect significantly muscle ATP, phosphocreatine and glycogen content. The insulinogenic index, i.e. the paired ratio between plasma insulin and blood D-glucose concentrations, displayed a paradoxical decrease during the intravenous glucose tolerance test. It was significantly lower in the creatine-supplemented rats both before and after glucose administration. The latter change was mainly attributable to a lowering of plasma insulin concentration. It is proposed, therefore, that creatine supplementation may improve the sensitivity to insulin in extrapancreatic sites in the present animal model of Type-2 diabetes.