A specific hemorheologic treatment might reduce urinary protein excretion and the decline in kidney function in diabetic patients with overt clinical nephropathy. Twenty-one insulin dependent (type I) diabetic patients were randomized and assigned to a treatment with conventional antihypertensive therapy (protocol I) or with pentoxifylline (Trental 400) (protocol II). A marked improvement of blood rheology pattern, together with a reduction of urinary albumin excretion rate and total urinary protein excretion rate, was demonstrated throughout a 1-year follow-up study with pentoxifylline. Furthermore a decrease of systolic and diastolic blood pressure levels was found during the treatment. The modification of these parameters was followed by a significant increase of creatinine clearance in each of the patients studied. The results obtained during pentoxifylline therapy were comparable to those obtained in patients treated with conventional antihypertensive drugs. Pentoxifylline may therefore be used in the treatment of advanced nephropathy in diabetic patients.