The goals of this study were to (i) develop a computational model of solute transport and oxygenation in the kidney of the female spontaneously hypertensive rat (SHR), and (ii) apply that model to investigate sex differences in nitric oxide (NO) levels in SHR and their effects on medullary oxygenation and oxidative stress. To accomplish these goals, we first measured NO synthase (NOS) NOS1 and NOS3 protein expression levels in the renal microvessels of male and female SHR. We found that the expression of both NOS1 and NOS3 is higher in the renal vasculature of females compared to males. To predict the implications of that finding on medullary oxygenation and oxidative stress levels, we developed a detailed computational model of the female SHR kidney. The model was based on a published male kidney model, and represents solute transport and the biochemical reactions among O2, NO, and superoxide (O2-) in the renal medulla. Model simulations conducted using both male and female SHR kidney models predicted significant radial gradients in interstitial fluid oxygen tension (PO2) and NO and O2- concentration in the outer medulla and upper inner medulla. The models also predicted that increases in endothelial NO-generating capacity, even when limited to specific vascular segments, may substantially raise medullary NO and oxygen tension levels. Other potential sex differences in SHR, including O2- production rate and anti-oxidant capacity, are predicted to significantly impact oxidative stress levels but effects on NO concentration and PO2 are limited.