Background and objective: Zoledronate has been reported to inhibit the proliferation, adhesion and migration of vascular smooth muscle cells. In the present study, we assessed whether systemic and local delivery of zoledronate would be sufficient to prevent intimal hyperplasia. Methods: Twenty-four male Sprague-Dawley rats were assigned into four groups: non-treated group, systemic zoledronate-treated group, local collagen-treated group and local zoledronate-treated group. All four groups underwent balloon injury to the right common carotid artery. The left uninjured carotid arteries of the non-treated group were considered as normal artery samples. Twenty-one days after arterial injury and treatment, the right and left common carotid arteries were fixed, sectioned, stained and measured by computer-aided image analysis. Results: At 3 weeks, there was a 59% reduction of the intima/media area ratio in the systemic zoledronate-treated group compared with the non-treated group (P < 0.01). There was an 87% reduction of the intima/media area ratio in the local zoledronate-treated group compared with the local collagen-treated group (P < 0.01). Conclusions: Both systemic and local delivery of zoledronate correspond to a significant reduction in intimal hyperplasia seen at 3 weeks. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.