The purpose of this study was to document the possible effect of solubilised erythrocytes on insulin-receptor binding and tyrosine kinase activity after 12 weeks of metformin administration to 13 healthy obese women with no history of diabetes and normal glucose as evaluated by conventional criteria. Subjects were given metformin 850 mg twice a day for 12 weeks. The results showed that plasma glucose response to an oral glucose challenge did not change following metformin, but that insulin response was significantly lower (p < 0.0001). In addition, both the number of insulin receptors and the tyrosine kinase activity per receptor of solubilised erythrocytes were significantly greater following metformin administration. Since both body weight and plasma glucose concentrations were similar before and after treatment, the effect of metformin on insulin-receptor binding and tyrosine kinase activity appeared to be independent of either of these variables. In summary, oral administration of metformin led to an increase in tyrosine kinase activity or erythrocyte insulin receptors, suggesting that such action occurs in the absence of any significant change in plasma glucose concentration.