The mechanisms underlying the development and prevention of diabetic nephropathy are still not fully understood. In the present study in the OLETF (Otsuka Long Evans Tokushima Fatty) model of type 2 diabetic rats we investigated whether renal hemodynamic abnormalities exist and whether they precede the onset of diabetes. Using OLETF rats in both prediabetic and diabetic stages we assessed autoregulatory responses of total renal blood flow (RBF), and of superficial (SBF) and deep renal cortical blood flow (DBF) to stepwise reductions of renal perfusion pressure (RPP) induced by a manual clamp on the abdominal aorta. During clamp-induced reductions of RPP by 10 or 20 mm Hg, RBF fell significantly more in OLETF rats than in lean controls [Long-Evans Tokushima Otsuka (LETO)] rats. Whereas SBF showed no significant changes in either OLETF rats or LETO rats during mild clamping, DBF decreased significantly more in OLETF rats than LETO rats. Reduced autoregulatory efficiency in OLETF rats was observed in both prediabetic and diabetic stages. Micropuncture studies showed that tubuloglomerular feedback (TGF) responses of stop flow pressure (P_sf) are reduced in prediabetic (-7.3 v.s -25.7%) as well as in diabetic OLETF rats compared to LETO control rats (-4.4 v.s. -18.8%). Renal corticotomy was performed to measure glomerular capillary pressure (P_gc) directly. P_gc of deep cortical glomeruli was higher than superficial glomerular P_gc in both strains of rats, but the difference was especially pronounced in OLETF rats (deep 78±2 v.s. superficial 57±4 mm Hg). This study demonstrates reduced autoregulatory adjustments and impaired TGF efficiency in prediabetic OLETF rats. Thus, abnormal renal blood flow regulation precedes the onset of diabetes and is especially pronounced in the deep cortical region.