Systemic inhibition of nitric oxide synthase (NOS) in streptozotocin-induced (STZ-induced) diabetic rats results in decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an increase in renal vascular resistance (RVR). However, the exact isoform of NOS involved in diabetic renal hyperfiltration has not been determined. This study was conducted to clarify whether NO derived from neuronal NOS is involved in diabetic renal hyperfiltration when using a selective inhibitor of neuronal NOS, 7-nitro indazole (7-NI). Continuous infusion of NG-nitro-L -arginine methyl ester (L-NAME) at 5 microg/kg/min ameliorated renal hyperfiltration, decreased RPF, and increased RVR in diabetic rats without affecting the mean arterial pressure (MAP). 7-NI administered intraperitoneally in diabetic rats significantly reduced GFR without affecting MAP, but the renal hyperfiltration was still observed after the administration of 7-NI. The combined administration of L-NAME after 7-NI caused a further decrease in GFR in diabetic rats and ultimately resulted in normalization of GFR. 7-NI did not change any parameters of renal hemodynamics in control rats. Urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was significantly increased in diabetic rats over values found in control rats. Our results suggested that a local inhibition of NO in the kidney was involved in the amelioration of diabetic renal hyperfiltration and that NO derived from neuronal NOS is involved, at least in part, in renal hyperfiltration in STZ-induced diabetic rats.