Aim To investigate the molecular mechanism of the Zhitai Capsule, which is a phelgm and stasis treating prescription, protecting vascular endothelial cells and against atherosclerosis. Methods 24 male New Zeland White rabbits were divided into four groups: the normal control group, the hypercholesterol group, the Gimfibrozil group and the Zhitai group. Four months later, the rabbits were killed and the aortas were fixed. Using NADPH diaphorase histochemistry and in situ hybridization, we have studied the activity and mRNA expression of nitric oxide synthase(NOS),as well as the mRNA expression of endothelin in aorta. Results The NOS activity in the aortas of Zhitai group (1.38±0.63) were significantly higher than that of hypercholesterol group(0.40±0.24)(P<0.01); that the NOS mRNA expression in the aortas of Zhitai group(1.38±0.48) were much higher than that of hypercholesterol group(1.00±0.00)(P<0.05); and that the NOS mRNA expression in the aortas of Zhitai group (2.43±0.53) were much lower than that of hypercholesterol group(3.33±0.82)(P<0.05). The Zhitai capsule can prevent the activity and mRNA expression of NOS in advanced atherosclerosis from decending, the mRNA expression of endothelin in advanced atherosclerosis from increasing, and decrease the lipid necrosis core. Conclusion Zhitai capsual’s antiatherosclerosis role was correlated with it′s effect on mRNA expression of nitric oxide synthase and endothelin.