Hyperphosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies reducing serum phosphate have been shown to reduce serum PTH and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-PP, on serum and urine chemistry, renal histology, and cardiac structure was examined in the uremic rat model, 5/6th nephrectomy rat (5/6th NX). Uremic rats in chronic renal failure were gavaged daily with 25 µM 2-PP. Over the course of a 5-week experiment, serum chemistry in untreated uremic rats, 2-PP treated uremic rats, and age-matched control rats with normal renal function were determined 2 times per week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once/week from 24-hour collections. 2-PP reduced serum phosphate 40% ±3% without affecting total serum Ca2+. Serum phosphate in untreated uremic rats progressively increased 17% over the 5-week experiment. During 5-week experiments, serum PTH increased 65%± 25% in untreated uremic rats, and decreased 70% ± 7% in uremic rats treated with 25 mM 2-PP. Creatinine clearance decreased 20% in untreated uremic rats compared to a 100% increase in 2-PP treated uremic rats. Urine protein decreased, and urine osmolality increased in uremic rats treated with 2-PP. The mechanism of the effect of 2-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca2+ absorption. Over the course of the 5-week treatment with 2-PP uremic animals treated with 2-PP had a 2% to 4% weight gain/week similar to the weight gain seen in age-matched control rats with normal renal function.