Rhein was conjugated with polyethylene glycol (PEG) and triphenyl phosphonium (TPP) which self-assembled into a micellar drug carrier. The mitochondria-targeted rhein-loaded micelles were evaluated for the treatment of osteoarthritis. Via the NRF2 activator role of rhein, improved anti-inflammatory and antioxidative effects were obtained and the level of reactive oxygen or nitrogen species were decreased in cell culture studies. This evidence concerns the gene NFE2L2 and osteoarthritis.