In insulin-dependent (type 1) diabetes mellitus, increasing peripheral insulin sensitivity might be a useful approach in controlling the process leading to beta cell destruction by reducing insulin output and thereby reducing the antigenicity associated with its release. The aim of this study was to investigate whether the use of a biguanide, Metformin, which has been suggested to increase insulin sensitivity, was capable of modifying the natural history of diabetes in a model of type 1 diabetes, the non-obese diabetic (NOD) mouse. Using age-, sex- and litter-matched groups, three groups of 32 animals each were treated with Metformin in their drinking water at a high dose of 200 mg/kg body weight and at a low dose of 20 mg/kg body weight; the third group of mice acted as controls. Diabetes incidence at 30 weeks of age was similar in all groups. No significant differences in the calculated index of insulitis were observed in treated or control animals. We conclude that Metformin does not affect the disease process leading to clinical diabetes in this animal model.