The glomerular functional and histologic alterations present in rats after 1 year of severe experimental diabetes mellitus were examined. Determination of single nephron function revealed a significant decline (27%) in glomerular plasma flow, primarily as a consequence of a significant increase in afferent arteriolar resistance. Single nephron filtration rate was not decreased proportionate to the decline in glomerular plasma flow, principally because of a significant increase (33%) in the ultrafiltration coefficient. As a result, single nephron filtration fraction was significantly increased by 24%. These functional changes in diabetic rats were similar to those observed after only 1 month of experimental diabetes; however, considerable progression in the glomerular histopathologic characteristics was evident in rats diabetic for 1 year. These changes were characterized by an increased glomerular mesangial matrix, focal glomerulosclerosis, and intense staining for rat IgG and C3 in mesangial regions. We propose that these histologic changes may be a consequence of long-term increases in the filtration fraction particularly associated with decreases in nephron blood flow, functional changes that may favor mesangial localization of phlogogenic macromolecules.