An amphiphilic graft copolymer, composed of poly(β-amino ester)-graft-poly(ethylene glycol) (PAE-g-PEG), was prepared as the drug carrier for treatment of rheumatoid arthritis (RA). PAE-g-PEG was synthesized through Michael addition polymerization and analyzed by 1H nuclear magnetic resonance (1H NMR). Owing to its amphiphilic property, PAE-g-PEG was self-assembled into spherical micelles (23 nm in diameter) in an aqueous environment Methotrexate, a hydrophobic drug for the treatment of RA, was physically loaded into the hydrophobic core of micelles by the dialysis method, resulting in high encapsulation efficiency (85.36%). Dynamic light scattering and transmission electron microscopy revealed that the micellar structure at pH 7.4 rapidly disassociated under the mildly acidic environment (pH < 6.5), mimicking the pathological condition of RA. Owing to the rapid disassociation of PAE-g-PEG micelles, methotrexate in the micelles was rapidly released under the mildly acidic condition. The micelles were non-toxic to and readily taken up by RAW 264.7 cells. When systemically administered into collagen-induced arthritis mice models, the pH-sensitive micelles effectively accumulated in inflamed joints, implying their high targetability to RA. Overall, PAE-g-PEG micelles might be useful as the carrier for targeting RA.