Recently, quantum dots derived from trace elements like cadmium and selenium have attracted widespread interest in biology and medicine. They are rapidly being used as novel tools for both diagnostic and therapeutic purposes. In this report, we evaluated the distribution of silica-coated cadmium selenide (CdSe) quantum dots (QDs) following intravenous injection into male Swiss albino mice as a model system for determining tissue localization using in vivo fluorescence and ex vivo elemental analysis by inductively coupled plasma optical emission spectroscopy (ICP-OES). Trioctylphosphine oxide-capped CdSe quantum dots were synthesized and rendered water soluble by overcoating with silica, using aminopropyl silane (APS) as silica precursor. ICP-OES was used to measure the cadmium content to indicate the concentration of QDs in blood, organs and excretion samples collected at predetermined time intervals. Meanwhile, the distribution and aggregation state of QDs in tissues were also investigated in cryosections of the organs by fluorescence microscopy. We have demonstrated that the liver and kidney were the main target organs for QDs. Our systematic investigation clearly shows that most of the QDs were metabolized in the liver and excreted via faeces and urine in vivo. A fraction of free QDs, maintaining their original form, could be filtered by glomerular capillaries and excreted via urine as small molecules within 5 days.