The effect of d-α -tocopherol on the progression of renal dysfunction was investigated in rats injected with adriamycin (ADR), a model of progressive glomerulosclerosis associated with the nephrotic syndrome. Treatment with d-α -tocopherol was started 1 day before or 1 day after ADR injections (BE-TOC or AF-TOC rats). When compared to rats without d-α -tocopherol treatment (ADR-CON rats), the serum total cholesterol and triglyceride levels were significantly lower in the BE-TOC and AF-TOC groups. In week 16, the LDL cholesterol level and the atherogenic index were both significantly lower in BE-TOC and AF-TOC rats than in ADR-CON rats. The urinary protein, serum creatinine, blood urea nitrogen, malondialdehyde, and systolic blood pressure levels as well as the glomerulosclerosis score were high in ADR-CON rats, and reduced in BE-TOC or AF-TOC rats. There were no significant differences in body weight and serum albumin between the three groups in week 16. It is concluded that d-α -tocopherol can improve hyperlipidemia and ameliorate glomerulosclerosis in rats with ADR-induced progressive renal failure. Thus, d-α -tocopherol may have the potential for clinical application to treat focal glomeruloscler