<i>Background:</i> Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains high which correlates with the magnitude of residual albuminuria. Use of vitamin D receptor activators, such as calcitriol and paricalcitol, is associated with improved sur- vival. A small study with paricalcitol showed reductions in albuminuria. The VITAL study tests the hypothesis whether paricalcitol persistently reduces albuminuria in diabetic subjects already receiving angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) therapy. <i>Methods:</i> Randomization in this double-blind trial is equal allocation to paricalcitol 1 μ/day, 2 μg/day, or placebo. Inclusion criteria include: a diagnosis of type 2 diabetes, urinary albumin/creatinine ratio (UACR) between 100–3,000 mg/g, estimated glomerular filtration rate (eGFR) between 15–90 ml/min/1.73 m², serum calcium <9.8 mg/dl, and parathyroid hormone (PTH) between 35–500 pg/ml. <i>Results:</i> Baseline characteristics of the 281 subjects are: 69% men, mean age 64.9 ± 10.4 years, eGFR 40.7 ± 16.7 ml/min, median UACR (interquartile range) 612.3 mg/g (281–1,181 mg/g) and PTH 98.4 ± 63.8 pg/ml. <i>Conclusion:</i> This trial will be the first clinical test of the hypothesis that paricalcitol possesses pleiotropic effects and can modulate albuminuria in the setting of ACEI and/or ARB therapy. Results will have important clinical implications and are expected in November 2009.