Background: This study investigates the effectiveness of extracorporeal shock wave (ECSW) in ameliorating inflammatory mediator expression and neointimal formation in a rat model of vascular injury. Methods and Results: Male Sprague-Dawley rats with left carotid artery (LCA) injury induced by balloon dilatation (BD; group 1) were compared with group 2 [LCA injury plus ECSW-181 (defined as 181 total shocks given in LCA at 0.011 mJ/mm 2 ) on day 2 post-LCA injury], and group 3 (normal controls). The rats in each group were further divided into 3 subgroups (n = 6, each) that were sacrificed on postoperative day 3, 7 and 14, respectively. The results demonstrated that, compared to groups 2 and 3, group 1 had significantly increased cellular expression of CD40, interleukin-18, and connexin 43 at each analyzed time point (all p ! 0.001). Additionally, LCCA macrophage (CD68) recruitment was substantially increased in group 1 compared to groups 2 and 3 (all p ! 0.001). Furthermore, LCA neointimal proliferation and media thickness were markedly higher in group 1 than in groups 2 and 3 on days 7 and 14 post-BD (all p ! 0.001). Conclusions: ECSW markedly attenuates inflammatory responses, proliferation of neointima and smooth muscle cells in a rat vascular injury model.