Diabetes and increased BP are believed to interact synergistically in the pathogenesis and progression of diabetic nephropathy. The present studies were performed to examine if there were differences in BP load and/or protective renal autoregulatory capacity between the obese diabetic ZSF1 (fa-fa^cp) rats and their lean controls. By ~26 weeks of age, ZSF1 (n=13) but not their lean controls (n=16) had developed substantial proteinuria (180±19 vs. 16±1.4 mg/24hrs) and glomerulosclerosis (19±2.4 vs. 0.6±0.2%; p<0.001). However, average ambient systolic BP by radiotelemetry (12 to 26 weeks of age) was modestly lower in ZSF1 than in lean controls (130±1.4 vs 137±1.7 mmHg, p<0.002), although the 24 hour BP power spectra showed a mild increase at frequencies < 0.1 Hz in the ZSF1. Autoregulatory capacity under anesthesia in response to step changes in perfusion pressure between 100-140 mmHg was similarly well preserved in both ZSF1 and lean controls at 16-18 weeks of age (autoregulatory indices < 0.1). Similarly, differences were not observed for dynamic autoregulation in conscious rats (transfer functions between BP [input] and RBF [output] using chronic transonic flow probes). Collectively, these data indicate that the pathogenesis of nephropathy in the ZSF1 model of type II diabetic nephropathy is largely independent of differences in systemic BP and/or its potential renal transmission. However, these data do not exclude the possibility that the diabetic milieu may alter the glomerular capillaries in the ZSF1 such that there is an enhanced local susceptibility to injury with even normal glomerular pressures.