The rat carotid injury model is the most widely used model to study the pathophysiology of neointimal hyperplasia as well as the value of novel therapeutic approaches to limit vasoproliferative diseases such as restenosis. For lesion assessment, the current gold standard of histomorphometry neither provides integral insight into the vascular lesion in vivo nor assesses of functional lesion-associated flow alterations and the time course of lesion development. To overcome these limitations, we applied and validated duplex sonography as a novel tool for comprehensive lesions assessment in vivo. Left rat common carotid arteries (CCA) were balloon injured. Duplex sonography was performed in both injured and noninjured CCAs before and up to 14 days postinjury. Sham-operated animals served as controls. The parameters determined were vessel lumen diameter as well as systolic and enddiastolic flow velocity, time-dependent lesion development, and intraand interobserver variability. Subsequently, the model was applied to validate the therapeutic effect of gene transfer into the vessel wall and compared with histomorphometry. We show that duplex sonography in the experimental carotid injury model allows accurate follow-up of lesion development in vivo with low intra-and interobserver variability. It can be easily adopted to assess the efficacy of therapeutic approaches even with limited technical experience and adds valuable functional data to mere postmortem histomorphometric analysis, thereby closing the gap between experimental approaches and clinical importance of vascular lesions. restenosis; rat model of carotid injury; lesion assessment; duplex sonography FOR OVER TWO DECADES, balloon angioplasty has evolved toward a secure and efficient treatment of coronary artery stenosis. However, the major problem of percutaneous coronary interventions remains to be the time-dependent development of restenosis within the dilated vessel (22). The pathophysiology of restenosis evolves within a complex background, including genetic susceptibility (7), distinct lesion characteristics, and systemic factors such as the presence of diabetes mellitus (8). Animal models have contributed considerably to our present understanding of vascular restenosis (16). Because of readily available molecular tools such as genomic databases and species-specific antibodies, the rat carotid injury model has evolved toward the most widely used animal system to evaluate both molecular and cellular mechanisms of the pathophysiology of vascular injury as well as to validate the therapeutic efficacy of novel therapeutic strategies to inhibit key mechanisms of restenosis (16). In this particular model, vascular injury is induced by complete deendothelialization by means of an inflated balloon catheter. The subsequently evolving lesion is usually characterized by histomorphometric analysis alone. Although this particular method enables histomorphometric lesion assessment, it does not provide valuable insights into time-dependent lesion development. In addition...