Aim To investigate the potential candidate genes related to extracellular matrix(ECM) which might play roles in atherosclerosis by microarray technology. Methods Sixteen male SD rats were randomly subjected to the following treatments: standard diet with saline injection i.p.(control group,n=8) or fat diet with vitamin D3 injection i.p.(containing 3% cholesterol,0.5% sodium cholate,5% refined sugar,10% lard,and 81.5% base feed)(model group,n=8).After 14 w,serum total cholesterol(TC) and triglyeride(TG) were detected.Thoracic aorta was stained with HE and a solution of oil red O to visualize the lesion area.Total RNA was isolated from the aorta for microarray to explore the differential gene expression profiling. Cathepsin D expression was measured by immunofluorescence and western blot. Results Compared with the control group,model group showed elevated serum TC and TG(both P<0.05) and aortic fibrous plaque formation.510 genes were up-regulated and 1 218 ones were down-regulated in aorta tissue of model group by DNA microarray analysis when compared with control group.Further immunohistochemistry and western blot analysis revealed cathepsin D protein expression was significantly increased in aorta of model group whereas normal group showed little or no immuno-detectable cathepsin D expression. Conclusion Cathepsin D might influence vascular remodeling,which plays an important role in As.