To determine the role of indoxyl sulfate in the progression of glomerular sclerosis, the serum level of indoxyl sulfate was measured in patients with uremia, and the effect of oral administration of indoxyl sulfate on renal function and renal histology was studied in subtotally nephrectomized uremic rats. Further, the effects of a low-protein diet and oral sorbent (AST-120) administration on the serum and urine levels of indoxyl sulfate were studied in different groups of subtotally nephrectomized uremic rats. We noted a marked elevation of serum level of indoxyl sulfate in the patients with uremia. The oral administration of indoxyl sulfate to the uremic rats increased the serum creatinine and blood urea nitrogen levels and decreased creatinine clearance, inulin clearance, and p-aminohippuric acid clearance. The glomerular sclerosis index in the indoxyl sulfate-administered uremic rats was higher than in the control uremic rats. A low-protein diet and AST-120 administration decreased the serum and urine levels of indoxyl sulfate, the blood urea nitrogen level, the urinary protein level, and the glomerular sclerosis index in the uremic rats as compared with those on a high-protein diet. Thus, indoxyl sulfate, a circulating uremic toxin, stimulated the progression of glomerular sclerosis in the uremic model. A low-protein diet and AST-120 reduced the serum and urine levels of indoxyl sulfate and suppressed the progression of glomerular sclerosis.