Objective:To investigate the effects of paeonol on aortic nuclear factor-kappaB ( NF-κB) activity and blood lipid levels in the rats with atherosclerosis ( AS) . Methods:The AS rat model was established by administration of high-fat diet and vitamin D3 ( i. p. ). The rats were divided into 5 groups (n=8) randomly, namely the normal group, model group, positive control group(simvasta-tin, 10 mg·kg-1 ) and paeonol groups with the dose of 20 and 10 mg·kg-1 , respectively. After the 4-week treatment, the serum of rats was collected to determine the lipid levels. The aortic pathologic changes of AS rats were observed under a microscope, and then graded, and aortic NF-κB activity was detected by an immunohistochemistry method. Results:Administration of paeonol improved the severity of aortic pathology in AS rats. The pathologic grade in the paeonol group (20 mg·kg-1 ) showed a significant difference com-pared with that in the model group (P<0. 05). Paeonol (20 and 10 mg·kg-1) markedly decreased the TG, TC and LDL-C levels in the serum of AS rats (P<0. 05 or P<0. 01). Meanwhile, paeonol significantly inhibited the aortic NF-κB activity(IOD value) with (1. 96 ± 0. 55) and (2. 50 ± 0. 80) in 20 and 10 mg·kg-1 group, respectively, which showed significant differences compared with that in the model group (P<0. 05 or P<0. 01). Conclusion:Paeonol shows certain therapeutic effect in AS rats, and the mechanisms may be related with the regulation of lipid mobilization and the inhibition of aortic NF-κB activity.