To determine the relationship of skin microangiopathy and other diabetic microvascular complications, we measured changes in skin blood flow after the administration of the prostacyclin (PGI2) analogue, beraprost sodium (BPS), in 82 patients with non-insulin-dependent diabetes mellitus and 20 healthy subjects. The diabetic patients had various degrees of retinopathy and nephropathy. Using laser Doppler flowmetry we measured skin blood flow at the dorsum of the right big toe at various times after the administration of 40 micrograms BPS and calculated the blood flow change (delta flux = peak flux--basal flux). We also determined the ankle pressure index (API), an ankle/brachial systolic pressure ratio. The basal blood flow was higher in healthy subjects than in diabetic patients (P < 0.001). BPS significantly increased blood flow in both diabetic patients and healthy subjects (P < 0.001). In all 102 subjects delta flux was positively correlated with the API (R = 0.40, P < 0.001). Despite no differences in API among the diabetic retinopathy and nephropathy subgroups, the delta flux in diabetic patients with progressive retinopathy and macroalbuminuria was significantly lower than in healthy subjects or in diabetic patients with less severe retinopathy and nephropathy (P < 0.05). The results suggested that BPS increases skin blood flow and the flow increase induced by BPS is related partly to the levels of API. The effect of BPS on skin blood flow decreased with an increases in the severity of retinopathy and nephropathy. Diabetic skin microangiopathy appears to coexist with other microvascular diabetic complications and may be proportional to their severity.