The objective of this study was to investigate theeffect of rhein lysinate (RHL) on monocyte adhesion and itsmechanism. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay was used to determine thegrowth inhibition by drugs. The monocyte chemoattractantprotein (MCP)-1 levels were assayed using MCP-1 ELISA. The expression of proteins was detected by Western blottinganalysis. The results indicated that RHL inhibited monocyteadhesion in a dose- and time-dependent manner. RHL(\20 lmol/L) and lipopolysaccharide (LPS) had no effecton viability of human umbilical vein endothelial cells. Therefore, 20 lmol/L RHL was selected for this study. RHLinhibited secretion ofMCP-1 induced by LPS and expressionof intercellular adhesion molecule (ICAM)-1 and vascularcell adhesion molecule (VCAM)-1. In the meantime, bothRHL and p38 inhibitor (SB203580) inhibited phosphorylationof p38 and mitogen-activated protein kinase-activatedprotein kinase-2 (MAPKAPK-2) and transcription andexpression of ICAM-1 and VCAM-1. In conclusion, RHLinhibits the transcription and expression of ICAM-1 andVCAM-1 by the p38/MAPKAPK-2 signaling pathway, andthe effect ofRHLon transcription and expression of ICAM-1and VCAM-1 is similar to p38 inhibitor. RHL could be aprophylactic drug for atherosclerosis.