Abstract : The aim of this work was to investigate the effects of depleted (DU) or enriched uranium (EU) and of cesium 137 (137Cs) on vitamin D3 biosynthetic pathway in liver, kidney and brain in rat. A chronic exposure with environmental doses of 137Cs and uranium could decrease the vitamin D active form level (1,25(OH)2D3) and lead to molecular modifications of cytochromes P450 (CYPs) enzymes involved in this metabolism and associated nuclear receptors. We demonstrated that both UA and UE contamination affected VDR (vitamin D receptor) and RXRα (retinoid X receptor alpha) expression, and consequently could modulate the expression of vitamin D target genes involved in calcium homeostasis in kidney (ecac1, Epithelials Ca2+ channel 1 et cabp-d28k, Calbindin-D28K). These results suggest that these effects could be due to the chemical toxicity of uranium. On the contrary, the main molecular targets of 137Cs are CYPs involved in Vitamin D3 biosynthesis (CYP2R1, CYP27B1) in liver and brain.