OBJECTIVE To elucidate the significance of ET in diabetic microvascular disease. RESEARCH DESIGN AND METHODS We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. RESULTS The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 ± 0.04 pM and 0.60 ± 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 ± 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 ± 0.05 pM [n = 9]). CONCLUSIONS These results suggest that plasma ET-1 is related to diabetic microvascular disease.