Aim To investigate the effects of losartan on oxidative stress and the contents of vascular smooth muscle cells(VSMC) and macrophages in aortic atheromatous plaques of apolipoprotein E gene-deficient(Apo E~(-/-)) mice. Methods Twenty seven Apo E~(-/-) mice were randomly divided into three groups: control group,low dose losartan group5 mg/(kg·d)] and high dose losartan group25 mg/(kg·d)].The period of administration was 20 weeks.Serum nitric oxide(NO),superoxide dismutase(SOD),malondialdehyde(MDA)and serum lipids were measured by routine biochemical method.Aortic paraffin slice were prepared for histomorphological observation.The contents of VSMC and macrophages were detected by immunological histochemical method. Results There were no significant difference in serum lipids among three groups.Comparing with the control group,serum NO levels of the two treatment groups were significantly increased(p<0.01),the activity of SOD was notably enhanced(p<0.01),content of MDA was markedly decreased(p<0.05 and p<0.01).There were also significant differences between the two treatment groups(p<0.01).The atheromatous plaques of the two treatment groups contained some thick fibrous caps and little lipid cores.The contents of VSMC in the two treatment groups were significantly higher than that of control group(p<0.01).On the contrary,macrophages were notably lower than that of control group(p<0.01).Meanwhile,there were also significant differences between the two treatment groups(p<0.01 and p<0.05). Conclusions Without affecting the serum lipids,losartan can attenuate oxidative stress in Apo E~(-/-) mice and stabilize atheromatous plaque by means of increasing the content of VSMC and reducing macrophages.