Percutaneous angioplasty is one of the most commonly used methods to treat stenotic arteries in which lumen size is critically reduced by the formation of atherosclerotic plaques. However this procedure often fails due to restenosis within 6 months following the intervention. Restenosis consists in the renarrowing of the vessel lumen caused by vascular lesions induced by the angioplasty. This activates an inflammatory response leading to vascular smooth muscle cell proliferation and migration as well as vascular remodelling and neointimal thickening. In this study, we demonstrated that in a mouse model of percutaneous angioplasty, the endocannabinoid system, via its receptors CB1 and CB2, plays a role in restenosis. CB1 blockade or CB2 activation, respectively, reduced inflammatory cell infiltration as well as vascular smooth muscle cell proliferation in restenotic lesions following vascular injury. Thus targeting the endocannabinoid system could offer a new therapeutic strategy against restenosis.