Abstract Growth factors have been implicated in the pathogenesis of restenosis (myointimal hyperplasia after coronary interventions). In this study, we examined the expression of insulin-like growth factor-I (IGF-1), IGF-1 receptor, and transforming growth factor-β (TGF-β) in atherosclerotic and normal rabbit iliac arteries following overstretch balloon angioplasty of the iliac arteries to create a vascular lesion. Animals were sacrificed at 0, 3, 7, 15 and 42 days post angioplasty. The iliac arteries were processed for immunocytochemical localization of IGF-1, IGF-1 receptor and TGF-β using colloidal gold and the data were quantitatively analyzed. IGF-1, IGF-1 receptor and TGF-β immunoreactivity were all significantly increased in atherosclerotic arteries compared to control at all of the time points examined. Following balloon angioplasty, the levels of IGF-1 and IGF-1 receptor increased significantly in both control and even further in hypercholesterolemic vessels. In control vessels, the IGF-1 levels returned to preintervention levels, while in atherosclerotic vessels, the levels of IGF-1 and IGF-1 receptor remained elevated. In addition, TGF-β levels in control vessels showed an initial rise in the first week following injury but then returned to baseline levels. In contrast, atherosclerotic vessels demonstrated a sustained expression of TGF-β. Thus, IGF-1 and TGF-β expression is different in normal vs. atherosclerotic vessels following vascular injury. The intensity of expression of IGF-1 and its receptor, which is not reduced at 42 days compared to 15 days following injury, support a role for IGF-1 in smooth muscle cell proliferation and migration. The sustained increase in TGF-β could facilitate extracellular matrix (ECM) accumulation. Local vascular therapy that is directed towards modulating the effects of IGF-1 and TGF-β could reduce restenosis.