Aim To explore whether atorvastatin inhibits HMGB1-induced vascular endothelial activation, and clarify the underlying molecular mechanism. Methods The cultured endothelial cells （EC） of rats were treated by Atorvastatin, HMGB1,TLR4-specific inhibitor CLI-095 with different concentrations. Leukocyte-endothelial adhesion was calculated as the proportion of the adherent neutrophils fluorescence intensity among the total added cells. RT-PCR and Western blot method were used to assay the expression of Toll like receptor 4（TLR4）, ICAM-1 , E-selectin mRNA and protein. DNA binding activity of NF-κB was measured by EMSA. Results Atorvastatin, at concentrations ranging from 0.1 to 10 μmol/L, effectively and in a dose-dependent manner inhibited HMGB1-induced ECs activation. Atorvastatin markedly suppressed TLR4 expression （P<0.05） in ECsIncubation of ECs with atorvastatin and CLI-095 reduced HMGB1-induced NF-κB p65 DNA binding activity and adhesion molecules （ICAM-1 and E-selectin） expression （P<0.05）. Conclusion Atorvastatin can attenuate HMGB1-induced vascular endothelial activation. The underlying mechanism may be connected with inhibition of TLR4/NF-κB-dependent signaling pathway induced leukocyte-endothelial adhesion.