Objective: The objective of this study was to investigate the duration of R-2* and R-2 enhancement in murine liver in vivo after administration of a single dose of 3 different iron oxide-based contrast agents. Materials and Methods: Murine liver R-2* and R-2 were quantified longitudinally postadministration of 2.5 mgFe/kg ferumoxides, 2.5 mgFe/kg ferumoxytol, 2.5 or 5 mgFe/kg feruglose, or saline over 50 days. Changes in R-2* and R-2 were evaluated histologically using Perl's staining and by atomic absorption spectrometry. Results: All 3 contrast agents significantly increased liver R-2* and R-2 4 hours after challenge. After 10 days, R-2* and R-2 for both the ferumoxides and ferumoxytol cohorts had recovered to saline control levels, whereas the faster R-2* and R-2 of the feruglose cohort was sustained and significantly faster than control at day 50. Histology revealed feruglose in both Kupffer and endothelial cells, whereas both ferumoxides and ferumoxytol were associated with the Kupffer cells. Conclusion: Compared with ferumosides and ferumoxytol, feruglose exhibits prolonged R-2* and R-2 enhancement of murine liver.