The elevated glomerular filtration rate that occurs in 25 to 40 percent of insulin-dependent diabetics has been proposed as having a role in the initiation and evolution of diabetic nephropathy. We report that both enhanced NO synthesis by ecNOS in afferent arterioles and glomerular endothelial cells and increased expression of IGF-1 receptor can cause glomerular hyperfiltration, and that upregulated expression of ICAM-1 can promote the intraglomerular infiltration of mononuclear cells, which were prevented by aldose reductase inhibitor. The results of United Kingdom Prospective Diabetes Study (UKPDS) will also be discussed.