Abstract : Diabetic nephropathy is associated with the dysfunction of proximal tubule cells. Insulin-like growth factor 1 (IGF-I) has also been considered to play an important role in the development of diabetic nephropathy. Ginsenosides have been used as a remedy for diabetes in Asian countries. Therefore, we examined the preventive effect of ginsenosides against high glucose-induced alteration of IGF-I secretion in the primary cultured proximal tubule cells. In present study, Ginseng saponin (GS) completely blocked high glucose-induced stimulation of IGF-I secretion in proximal tubule cells, whereas panaxatriol (PT) and panaxadiol (PD) partially suppressed. In addition, high glucose stimulated cAMP formation and protein kinase C (PKC) activity from cytosolic to membrane fraction. GS completely prevented high glucose-induced stimulation of cAMP and PKC activity while PT and PD partially did. Furthermore, high glucose-induced stimulation of IGF-I was blocked by the treatment of PKI (protein kinase A inhibitor) and bisindolylmaleimide I (protein kinase C inhibitor). In conclusion, GS prevented high glucose-induced dysfunction of proximal tubule cells. Key words : Ginsenosides, diabetic nephropathy, proximal tubule cells, IGF-I, cAMP, protein kinase C