Objective To investigate the role of matrix metalloproteinase-9(MMP-9) in the formation of isolated systolic hypertension so as to provide a new model of isolated systolic hypertension. Methods Twenty 8-week old male Wistar rats were randomly divided into the model group (n=10) and control group(n=10). To induce large artery calcification, rats were treated with warfarin and vitamin K1. Eight weeks later, blood pressure and left ventricular pressure were measured by right carotid arterial cannulation. The segments from each aorta were processed for histological analysis by Von Kossa methed. Aortic calcium contents were calculated in each group with atom-spectrum. Elastic fiber structure in aorta was analyzed by elastic fiber staining. MMP-9 expression was determined by immunohistochemistry and Western blot. Results Compared with control group, blood pressures were significantly higher in model group[systolic blood pressure: (151±9) vs (113±7)mmHg, P＜0.01; diastolic blood pressure: (122±10) vs (98±8)mmHg, P＜0.05]. The mean left ventricular pressure was not significantly different between the two groups. In model group, the blood pressure fluctuation was associated with morphological change of the aorta, such as extensive arterial medial elastocalcinosis. Compared with control group, calcium content in aorta was significantly higher in model group [(17.9±1.8) vs (5.8±0.6)mg/g, P＜0.01]; the elastic lamellae was flatten and lost natural waviness. Western blot analysis showed that MMP-9 protein expression level was significantly higher in model group than in control group. Conclusion Chronic treatment with warfarin and vitamin K1 produce a satisfactory model of isolated systolic hypertension which is identical to the disorder in humans. The elevated expression of MMP-9 enhances the elastin degeneration and calcification of the aortic elastic fibers and plays a role in the formation of isolated systolic hypertension.