PVA coated and fluorescent dye (Cy3.5) functionalized vinyl alcohol/vinyl amine copolymer coated superparamagnetic iron oxide nanoparticles (SPION) were evaluated for systemic distribution and elimination after intraarticular injection in sheep. Observation was done at 3, 24, 72, and 120 hours after injection using light microscopy, fluorescent microscopy, and confocal microscopy. No pathologic influence of SPION on the tissue harvested could be seen. A significantly increased iron content could be identified in the kidneys, lymph nodes, and spleen after injection of SPION. No particles were detected in the liver, the urinary, and the gall bladder. No positive fluorescent signal could be attributed to SPION throughout the organs. Our results indicated that the iron component of the SPION is possible to be incorporated into the physiologic iron metabolism after reabsorption in the proximal tubule system of the kidney and that concentration levels of Cy3.5 are too low to be detected throughout the body.