Aim To compare the effects of intermittent and constant high glucose media on the production of vascular relaxing factors in cultured human umbilical vein endothelial cells(hUVEC). Methods hUVEC were grown to confluence and were exposed for 7 days to 5 mmol/L glucose(normal control),20 mmol/L glucose(constant high glucose) and 5 mmol/L alternating with 20 mmol/L glucose(intermittent high glucose) on a daily basis.The concentration of 6-keto-PGF1α(the stable hydrolysed product of prostacyclin) was determined by radioimmunoassay,the nitric oxide(NO) was measured by means of Griess reaction and the malondialdehyde(MDA) content was detected by the method described by Schuh. Results Both the 6-Keto-PGF1α and NO in intermittent high glucose group were significantly lower than that in constant high glucose group(21±6 ng/L vs 36±8 ng/L,p<0.01;13.6±2.0 mmol/L vs 18.2±3.7 mmol/L,p<0.001 respectively).However,the intermittent glucose group had increased MDA(16.5±2.7 mmol/L vs 13.2±2.2 mmol/L,p<0.05) compared with constant glucose group. Conclusion These findings suggest that variability in glycemic control could be more deleterious to endothelial cells.