Tissue fibrosis is an important index of renal disease progression. Diffusion-weighted magnetic resonance imaging's (DWI-MRI) apparent diffusion coefficient (ADC) reveals water diffusion is unobstructed by microstructural alterations like fibrosis. We hypothesized that ADC may indicate renal injury and response to therapy in patients with renovascular disease (RVD). RVD patients were treated with medical therapy (MT) and percutaneous transluminal renal angioplasty (MT + PTRA) (n = 11, 3 bilaterally, n = 14 kidneys) or MT (n = 9). ADC and renal hypoxia (R2*) by blood-oxygen-level-dependent MRI were studied before (n = 27) and 3 months after (n = 20) treatment. Twelve patients underwent renal biopsies. Baseline ADC values were correlated with changes in eGFR, serum creatinine (SCr), systolic blood pressure (SBP), renal hypoxia, and renal vein levels of pro-inflammatory marker tumor necrosis-factor (TNF)-α. Renal oxygenation, eGFR, and SCr improved after MT + PTRA. ADC inversely correlated with the histological degree of renal fibrosis, but remained unchanged after MT or MT + PTRA. Basal ADC values correlated modestly with change in SBP, but not in renal hypoxia, TNF-α levels, or renal function. Lower ADC potentially reflects renal injury in RVD patients, but does not change in response to medical or interventional therapy over 3 months. Future studies need to pinpoint indices of kidney recovery potential.