Background and Objectives: Local delivery of drugs to the arterial wall represents a strategy for the treatment of fibroproliferative vascular disease. Paclitaxel has been shown to inhibit vascular smooth muscle cell proliferation and migration contributing to neointimal formation. This study tested whether perivascular delivery of paclitaxel can prevent neointimal formation in a rat carotid artery injury model. Materials and Methods: The ability of locally-administered paclitaxel to prevent the neointimal hyperplastic response was tested by incorporating 10 關g paclitaxel into 40% F-127 pluronic gel which were applied to the adventitial surface of the rat carotid artery immediately following balloon injury. Fourteen days after angioplasty, neointimal growth was compared between paclitaxel-treated rats (n=12) and rats treated with pluronic gel only (control group, n=11). Results: Paclitaxel-treated group showed significant neointimal formation reductions versus the control group (0.10 짹 0.05 mm² versus 0.21 짹 0.05 mm², p<0.05). Perivascular application of paclitaxel produced a highly localized pattern of inhibition of neointimal growth in the arterial cross-section. Although 10 關g of paclitaxel did not show significant cytotoxicity, 20 關g of paclitaxel (n=3) demonstrated cytotoxicity with medial cell drop out in the region of application. Conclusion: We have demonstrated that local extravascular application of 40% F-127 pluronic gel containing paclitaxel provides an effective mechanism for inhibiting the proliferative response to vascular injury in the rat. The cellular response to paclitaxel is highly focal. Local sustained delivery of paclitaxel as little as 10 關g was effective in preventing neointimal growth without destroying medial wall smooth muscle cells.