To investigate the effect of the antihyperglycemic drug metformin on glucose transporter protein and gene expression, skin fibroblasts obtained from normal and diabetic volunteers were grown in culture and incubated with metformin at various concentration for up to 16 days. Metformin caused a dose and time dependent increase in GLUT1 number with a maximum at a concentration of 10 micrograms metformin given over 4 days. This was accompanied by an increase in GLUT1 mRNA, suggesting that metformin has a stimulating effect on glucose transporter gene expression. No significant difference was observed between cells obtained from type II diabetic patients and those from controls. We conclude that in human fibroblasts GLUT1 de novo synthesis is involved in the long term effect of metformin on glucose transport.