Clinical and experimental studies indicate that low-molecular-weight heparins reduce inflammation. To uncover the possible mechanisms involved, we investigated the effect of a low-molecular-weight heparin, enoxaparin, on high glucose-induced activation of endothelial cells. Bovine valvular endothelial cells and human endothelial cell line, EA hy926 were cultured in medium containing 5 mM (normal glucose) or 33 mM (high glucose) glucose. Postconfluency, the cells were exposed for 48 h to high glucose in the absence or presence of 16 microg/ml enoxaparin and tested for monocyte adhesion, expression of cell adhesion molecules, and translocation of nuclear transcription factor-kappaB (NF-kappaB), using adhesion assays, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Statistical data revealed that treatment with enoxaparin resulted in a significant decrease in monocyte adhesion, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, translocation of NF-kappaB, as well as in the level of intracellular reactive oxygen species. These results suggest that enoxaparin reduces the high glucose-induced activation of endothelial cells by inhibiting monocyte adhesion through a mechanism that involves cell adhesion molecules and NF-kappaB.