Context: DTD is a Chinese herb prescription used for centuries to treat atherosclerosis or dizziness. Previous studies show that DTD could inhibit ICAM-1 expression induced by 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 expression of p53 and p21. Materials and methods: The rats were orally treated with DTD for 3 d (2.3 g/kg per day), and then the serum was collected. HUVECs were cultured and stimulated by TNF-alpha with or without DTD serum (5, 10, and 20%). The expression of ICAM-1 mRNA was examined by RT-PCR and the expression of p53 and p21 was examined by western blot analysis. Results: The ICAM-1 mRNA levels induced by TNF-alpha were significantly reduced from 23 to 47%, and the expression of p53 and p21 mRNA levels were significantly reduced from 13 to 43% and 14 to 42%, as the concentration of DTD serum increased. In western blot, TNF-alpha-induced the expression of p53 and was inhibited from 15 to 53%, by DTD serum in a concentration-dependent manner. TNF-alpha-induced expression of p21 was inhibited from 2 to 37%, by DTD serum in a concentration-dependent manner. Discussion and conclusion: DTD has a function of "dissolving phlegm'', thus it is chosen for the treatment of atherosclerosis. This study demonstrated that DTD could significantly inhibit the expression of ICAM-1, p53 and p21, which are important factors of atherosclerosis. Therefore, the present study indicates the pharmacological basis for treatment of atherosclerosis with DTD.