Background: Paclitaxel has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal formation, at nanomolar levels in vitro. In vivo, paclitaxel inhibited neointimal formation in the rat carotid artery after endothelial denudation injury, at plasma levels approximately 100 to 1,000 times lower than the concentrations used in treating neoplasms. Peak levels achieved in this model were approximately 50-60 nM. This study tested whether novel oral formulations of paclitaxel can prevent neointimal formation in a rat carotid artery injury model. Methods and Results: Oral formulations of paclitaxel (0, 5, 7.5, or 10 mg/kg) were given to 40 rats by gavage for 5 days after injury. The peak levels of paclitaxel of 5, 7.5, and 10 mg/kg were 61짹16, 89짹22, and 108짹28 nM, respectively. Treatment effects were assessed 11 days after injury. The angiographic minimum luminal diameters of the oral paclitaxel-treated groups (5, 7.5, 10 mg/kg; 6.28짹2.09, 6.97짹1.79, 7.97짹1.57 arbitrary unit) were significantly larger than that of the control group (4.67짹1.45 a.u.). The oral paclitaxel-treated groups (5, 7.5, 10 mg/kg; 0.05짹0.05, 0.04짹0.03, 0.05짹0.03 mm²) showed significant reductions of neointimal formation compared to the control group (0.13짹0.05 mm²). All rats survived to completion of the study. Only 2 animals which were 10 mg/kg group experienced weight lose (���10%) and loose stool between 4 to 6 days after injury. All other animals appeared healthy during the study. For comparison, intraperitoneal formulations of paclitaxel (0 or 2 mg/kg) were given by intraperitoneal injection to 15 rats. And we confirmed that intraperitoneal administration of paclitaxel was also effective to inhibit neointimal formation. Conclusion: Oral formulations of paclitaxel provide an effective method for inhibiting the proliferative response to vascular injury in the rat. Oral formulations of paclitaxel could be useful for multiple lesions with or without stents. In addition, adjunctive doses could be implemented for the prevention of late neointimal catch-up.