Aim To observe the effects of angiotensinⅡ type-1 receptor antagonist losartan on the neointimal proliferation and expression of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2) after balloon angioplasty in Rabbits. Methods Twenty four rabbits were randomly divided into three groups: control group, model group and Losartan group. The rabbits of the latter two groups were fed with a 1.5% cholesterol diet starting one week before balloon injury. Then they were underwent ballon angioplasty in the celiac artery after the nine weeks of cholesterol diet. The losartan group was orally given losartan(10 mg/kg per day ) starting one week before angioplasty. Then the arteries were prepared for histological observation. Also, the sections were stained for MMP-2 and TIMP-2 immunohistochemistrical analysis. Results We found that after nine weeks of high-cholesterol diet, the serum total cholesterol and low density lipoprotein cholesterol levels of the model, losartan groups were significantly increased (p<0.01), and there were no changes in blood lipid parameters after losartan treatment. At the end of 13 weeks, compared with the model group, the intimal area (IA), intimal thickness (IT), IT/MT ratio (MT:media thickness),IA/MA ratio (MA:media area) of the losartan group were significantly decreased about 65%, 34%, 32%, 28%, respectively (p<0.01). Immunohistochemistrical analysis showed that there were no significant changes in the expression of MMP-2 after losartan treatment, while the expression of TIMP-2 significantly lowered, and the ratio of MMP-2/TIMP-2 significantly increased as a result of losartan treatment. Conclusion Losartan could significantly inhibit intimal proliferation during the restenosis after balloon injury without affecting blood lipid level; The mechanism of anti-resterosis by losartan may be related to inhibition of TIMP-2 and the revertion of balance of MMP-2/TIMP-2.