Context: Dao-Tan decoction (DTD) is a Chinese herb prescription used to treat atherosclerosis or dizziness for centuries. Previous study shows that DTD could inhibit intercellular adhesion molecule-1 (ICAM-1) expression induced by tumor necrosis factor-alpha (TNF-alpha). However, its mechanism has never been clearly described. Objective: To examine the hypothesis that DTD might inhibit TNF-alpha-induced ICAM-1 expression through regulating the mitogen-activated protein kinase (MAPK) pathways, involving Jun N-terminal kinase (JNK) and p38. Materials and methods: The rats were orally administrated with DTD for 3 days (2.3 g/kg per day), then the serum was collected. Human umbilical vein endothelial cells (HUVECs) were cultured and stimulated by TNF-alpha with or without DTD serum. The expression of ICAM-1 mRNA was examined by reverse transcription-polymerase chain reaction and the expression of p38 and JNK was examined by Western blot analysis. Results: DTD serum significantly inhibits TNF-alpha-induced ICAM-1 expression by 17-41% on HUVECs. TNF-alpha-induced JNK and p38 activations, which were involved in ICAM-1 expression, were significantly inhibited with DTD serum treatment by 10-50% on HUVEC. Discussion and conclusion: Based on the theory of traditional Chinese medicine (TCM), pathogenesis of atherosclerosis is caused by "blood" and "phlegm" attached on blood vessels. DTD has a function of "dissolving phlegm", thus it is chosen for the treatment of atherosclerosis. This study demonstrated that DTD could inhibit the expression of ICAM-1, by significantly preventing the activation of JNK and p38, which are important factors of atherosclerosis. Therefore, the present study indicates the pharmacological basis for treatment of atherosclerosis with DTD.