Coating superparamagnetic iron oxide (SPIO) with dextran increases the stability of the magnetic nanoparticles during blood circulation, yet this is accompanied by an increase in the particle size and the vascular permeability efficiency of the SPIO nanoparticles into the joints decreases. In our study, the thickness of the dextran coated onto SPIO (dex-SPIO) was optimized without affecting the magnetic quality of iron oxide by adding a suitable amount of glucose into the crystal growth process. To further improve the signal enhancement effect of this glucose and dextran coated SPIO (glu-dex-SPIO) for the detection of the inflammatory site of arthritis, folic acid (FA) was conjugated to glu-dex-SPIO. This FA glu-dex-SPIO was used as a negative contrast agent for MRI to visualize the antigen induce arthritis (AIA) model in rats using a 7 T MR scans. MR imaging revealed more significant differences between the synovium and surrounding tissues with FA glu-dex-SPIO than when using the non-targeting glu-dex-SPIO over a long period of time (24 h) after intravenous injection. Moreover, the therapeutic efficacy of the cyclooxygenase 2 (COX-2) inhibitor treatment of the inflamed joints also could be confirmed by using FA glu-dex-SPIO enhanced MRI, indicating that this type of nanoparticles could also have potential as a contrast agent for measuring the treatment response of rheumatoid arthritis.