Loss of renal mass in rats with experimental diabetes mellitus leads to exaggerated hypertrophy of remaining nephrons and accelerated diabetic glomerulopathy. To examine factors responsible for glomerular injury in this setting, rats with preexisting diabetes were subjected to unilateral nephrectomy. Micropuncture studies and evaluation of glomerular morphology were performed 2-3 mo later. Nephrectomized diabetic rats demonstrated significant increases in kidney weight, superficial nephron glomerular filtration rate, and superficial nephron plasma flow compared with two-kidney diabetic rats and nephrectomized nondiabetic controls. Glomerular capillary hydraulic pressure was comparable in two-kidney and nephrectomized diabetic rats and was significantly reduced compared with nephrectomized nondiabetic controls. Nephrectomized diabetic rats demonstrated significant albuminuria, mesangial matrix expansion, and focal glomerulosclerosis, whereas two-kidney diabetic rats and nephrectomized nondiabetic controls showed only minimal alterations in glomerular morphology. It is concluded that diabetic rats can undergo glomerular functional compensation in response to nephron loss. Moreover, accelerated glomerular injury caused by nephron loss in diabetic rats could not be attributed to increased glomerular capillary pressure.