Diabetic nephropathy is characterized by specific morphological changes and impairment of renal hemodynamics. To determine whether diabetic nephripathy could be improved by improvement of renal hemodynamics, 80μg/day of prostaglandin E(1) (PGE(1)) was administered daily for 4 weeks to 19 non-insulin-dependent diabetic inpatients with overt proteinuria. In 6 patients who initialy had daily urinary protein (UP) values above 3.5g/day, the UP value was sinificantly reduced by PGE(1) administration (p<0.05). However, in 6 patients who initially had UP values above 200mg/day and below 3.5g/day, the UP value was unchanged. In the former group, creatinine clearance was significantly reduced during PGE(1) administration (p<0.05), but was restored after termination of PGE1 adminstration (ns). Serum creatinine, serum total protein and serum albumin values were unchanged by PGE(1) administration in both groups. One petient who had a UP level above 200mg/day showed marked improvement on his renogram during PGE(1) administration and in 7 patiests who had UP values below 200mg/day, the ratio of plasma renin activity 120 minutes after furosemide injection in an upright posture to that of basal condition (PRA120/0) was significantly reduced. These findings inducate that PGE(1) increased renal blood flow, and suggest that improvement of renal hemodynamics is an important method of therapy for diabetic nephropathy with overt proteinuria.