We investigated the role of arginine vasopressin (AVP) in the development of diabetic nephropathy and the effect of specific vasopressin V1 receptor antagonist of 1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone (CAS 131631-89-5, OPC-21268) on albuminuria in patients with non-insulin dependent diabetes mellitus. Basal levels of AVP in diabetic patients showing microalbuminuria were significantly high compared to diabetics without any complications, suggesting that in those patients abnormally high amounts of AVP seem to be secreted. Three-week treatment with OPC-21268 demonstrated that albuminuria significantly decreased without affecting renal function. Increased secretion of AVP may induce proliferation of renal mesangial cells and modify blood flows in the glomerular capillaries. The present data suggest that OPC-21268 may be useful for preventing the development of diabetic nephropathy, although its long-term effects should be examined. In conclusion, AVP may play a crucial role in the pathophysiology of diabetic nephropathy and that OPC-21268 seems to prevent further progression of nephropathy in non-insulin dependent diabetes mellitus.