Aim To investigate whether thrombin could activate the signaling pathway-nuclear faclor-κB (NF-κB) and upregulate the expression of matrix metalloproteinase-2 (MMP-2) on human umbilical vein endothelical cellls (hUVEC) in vitro. Methods hUVEC was stimulated with thrombin, adding to hirudin and heparin according to separate groups. Immunocy tochemistry and Western blot analyses were used to detect the activation of NF-κB, which means the transfer of NF-KB from cyto plasina to nucleus. The expression of MMP-2 was determined with reverse transcriptase-polymerase chain reactin (RT-PCR).Results It was found that tlirombin could rapidly induce the activation of NF-KB in hUVEC. Baseline NF-icB nuclear binding in hUVEC increase by more than 14. 13% and 31.29% at 15 min and 30 min respectively. Thrombin significantly increased MMP-2 mRNA expression and production in hUVEC with time-dependent pattern (1-48 h). Hirudin was able to inhibit the activation of NF-κB and expression of MMP-2 in hUVEC. Conclusion Thrombin could activate the signal pathway-NF-κB and had remarkable effect on hUVEC expression of MMP-2, which may thereby influence the pathogenesis of atherosclerosis.