The protective effect of phosphate binder (PB) on nephropathy was examined in spontaneously hypertensive rats with non-insulin-dependent diabetes mellitus (NIDDM) fed a high-protein diet. The rats were treated with vehicle or streptozocin neonatally. After 14 weeks, all rats were fed a high-protein diet (50% protein content), and in half of the diabetic rats the diets were supplemented with PB. At 24 weeks, the urinary excretion rate of albumin and kidney weight increased in diabetic rats, but decreased or tended to decrease in diabetic rats treated with PB. The elevation of urinary excretion rate of N-acetyl-beta-D-glucosaminidase, probably due to protein load, was also abolished with PB.