Background: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects including anti-inflammatory and anti-atherothrombotic activities. We wanted to study the underlying mechanism of these activities. Methods: Human umbilical vein endothelial cell (HUVEC) was treated with tumor necrosis factor (TNF)-慣(10 ng/mL) alone or with rosuvastatin (30 關M). The extent of inflammation was determined by U937 monocyte adhesion assay. Protein levels and mRNA levels of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, IL-8, and cyclooxygenase (COX)-2 were determined by reverse trancriptase-polymerase chain reaction (RT-PCR), ELISA, and immunoblotting. Expressions or activations of c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), p38 kinase, Akt, and signal transducer and activator of transcription (STAT)-3 were determined by immunoblotting. Results: Rosuvastatin decreased the extent of U937 monocyte adhesion to TNF-慣-stimulated HUVEC by 23.5%. Rosuvastatin inhibited mRNA expressions of ICAM-1, MCP-1, IL-6, and COX-2, and protein expressions of ICAM-1, IL-6, IL-8, and COX-2 in TNF-慣-stimulated HUVEC. JNK phosphorylation induced by TNF-慣 was also attenuated by rosuvastatin pretreatment. However, phosphorylated ERK and p38, bcl-2 expressions were not affected by the rosuvastatin. Activities of Akt and STAT-3 were rescued by pretreatment of rosuvastatin in 24 hours. Conclusions: This study suggests the beneficial effects of rosuvastatin can be resulted from the inhibition of ICAM-1, MCP-1, IL-6, IL-8, COX-2, and JNK, as well as the preservation of activities of Akt and STAT-3.