Objective To investigate the possible signal transduction pathways involved in the low shear stress-induced up-regulation of IL-8 mRNA expression in cultured human umbilical vein endothelial cells (HUVECs). Methods LightCyclerTM system was employed to assay the expression of IL-8 mRNA of HUVECs. The results were compared with each among the groups stimulated by low shear stress (4.20 dyne/cm^2) with/without kinds of inhibitors. Results (1)HUVECs pre-treated with cAMP-dependent protein kinase inhibitor (KT5720), or phospholipase C inhibitor (neomycin), or tyrosine protein kinase inhibitor (tyrphostin-25) partially inhibited the low shear stress-induced up-regulation of IL-8 mRNA expression; (2) EGTA or the intracellular Ca(superscript 2+) chelator BATPA/AM or verapamil, a Ca(superscript 2+) channel blocker, also partially suppressed up-regulation of IL-8 gene induced by low shear stress; (3) G protein was involved in the low shear stressinduced IL-8 mRNA expression; (4) HUVECs pre-treated with cGMP-dependent protein kinase inhibitor (KT5823) had no effect on such gene expression. Conclusions (1) There are several signal molecules, for example, the protein kinase C, Ca(superscript 2+), and so on involved in up-regulation of IL-8 mRNA expression induced by low shear stress. (2) Activation of G protein is necessary.