The effect of size and coating material on the pharmacokinetics and biodistribution of iron oxide particles are well documented. However, the effect of these parameters on liver metabolism has yet to be investigated. The current work focuses on investigating how the physical and chemical properties of iron oxide particles influences degradation and excretion. Since most iron oxide based contrast agents are used as molecular imaging probes for Magnetic Resonance Imaging (MRI), focus is placed upon the effect of degradation on the in- vivo MR liver signal. Additionally, this work also provides insight into the relaxation theory associated with iron oxides. Although contrary to current theories surrounding intracellular iron metabolism, the current work highlights the fact that it is the coating material and not the cellular distribution that influences the rate of particle degradation. Since methods enabling accurate determination of iron oxide concentration in the liver are limited (due to high endogenous iron levels), this work also provides validated techniques to determine the rates of liver clearance and metabolism.