Aim To study how Hcy leaded to NF-κB activation and induced endothelial inflammation and how simvastatin antagonized the inflammatory response. Methods Human umbilical vein endothelial cells (hUVEC) were treated with Hcy, with or without simvastatin, for different times. Dynamic changes of NF-κB activation were measured by electrophoretic mobility shift assay (EMSA), TransAMTM NF-κB P65 assay system. Western blotting was performed to detect inflammatory proteins expression respectively. Results Treatment with both low (0.5 mmol/L) and high (3.0 mmol/L) concentrations of Hcy induced hUVEC NF-κB activation was accompanied by an increased level of MMP-2, MMP-9 and IL-1β expression. The NF-κB activation reached its maximum at 30 min and 6 h induced by high (3.0 mmol/L) concentrations of Hcy. EMSA and Western blotting showed Hcy induced NF-κB activation due to the increased phosphorylation of the inhibitory protein (IκBα) as well as the degradation of IκBα, while simvastatin almost completely blocked the NF-κB activation as well as the phosphorylation and degradation of IκBα. Conclusion Hcy may induce hUVEC inflammation via a pathway involving IκBα and NF-κB and simvastatin can inhibit homocyteine-induced endothelial dysfunction and inflammatory response.