Iodine deficiency (ID), which still affects almost two billion persons worldwide nowadays, has been associated to the incidence of several pathologies. In breast, animal studies showed that ID induces oxidative stress, structural and functional alterations and increases its sensitivity towards carcinogens. A protective role against breast cancer was also attributed to iodide. Besides, ID induces a vascular activation in thyroid, salivary glands and stomach, other iodide uptaking organs. Since angiogenesis is an important step in tumor progression and since the sodium/iodide symporter (NIS) is overexpressed in 80% of breast cancers, we have studied the vascular effects of ID in vivo and in a cancerous (MCF7) and a non-cancerous (MCF12A) breast cell line. Eight week NMRI mice were fed with iodide deficient diet and perchlorate (NIS inhibitor) containing water during 0 to 10 days, with or without bevacizumab (VEGF inhibitor) injection. Breast blood flow was measured with a laser Doppler in mice anesthetized with ketamine (80 mg/kg, ip) and xylasine (12 mg/kg, ip). Cells were grown in culture medium containing iodine. Medium was then changed for iodine-containing (control) or deficient (ID) medium for 2 to 8 hours. Values are given as mean±SEM, compared by a one-way ANOVA followed by a multiple comparison post hoc tests. In vivo, increased VEGF expression was observed by immunohistochemistry in the stroma and in epithelial cells from 1 to 2 days of ID (N=8) and a significant VEGF-dependent increase in mammary glands blood flow was observed after one day of ID treatment (134.1±5.1% of control (100±4.1%)). Blood flow then decreased from day 2 to day 10 to values not significantly different from control. The pathway leading to VEGF activation was then studied in cell culture. In MCF7 cells, ID induced a transient increase in reactive oxygen species (ROS) observed with a DCFH- DA fluorescent dye (N=5) after 2 hours. It was followed by an increase in the expression of hypoxia induced factor 1a (HIF-1α) protein (Western blot, N=5) as well as VEGF mRNA (qPCR, 146.5±11,8% of the control (100±4%)) after 4 hours. The increased HIF-1α protein and VEGF mRNA were inhibited by N-acetylcysteine, a ROS inhibitor, and by rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. However, mTOR activity was not inhibited by N-acetylcysteine. In MCF12A cells, ID induced a transient increase in ROS. A mTOR and ROS-dependent increase in VEGF mRNA (qPCR, 184.3±19.3% of the control (100±4.1)) was observed after 3 hours of ID. These data indicate that breast cells induce a vascular activation when exposed to ID through a VEGF overexpression, which is usually associated to a bad prognosis in cancers, and via ROS and mTOR signaling, which is a key regulator of cell cycle. This work could thus help understanding the established correlation between ID and breast pathologies, among which cancers.