To determine whether a decrease in prostacyclin production is involved in the increase in endothelial permeability induced by a high concentration of glucose, we evaluated the effect of beraprost sodium, a stable prostacyclin analog, on the transendothelial permeation of albumin in cultured aortic cells. Permeation of albumin across an endothelial cell monolayer was significantly greater when the cells were cultured with a high concentration of glucose (400 or 800 mg/dl) than when they were cultured with 100 mg/dl glucose. No significant change in the permeation of albumin was observed when cells were cultured with 100 mg/dl glucose as compared with 100 mg/dl glucose plus 700 mg/dl mannitol. The addition of beraprost sodium to the culture medium completely restored the increase in the permeation of albumin brought about by 400 mg/dl glucose. These results suggest that increased transendothelial permeation of albumin by high glucose may be due in part to a decrease in prostacyclin production by the endothelial cells. Beraprost sodium may restore the endothelial barrier function affected by a high concentration of glucose.