Tumor necrosis factor (TNF) antagonists, including etanercept, have been approved for the treatment of rheumatoid arthritis (RA). These agents are not free of adverse events like other antirheumatic agents. Several important adverse events in CNS lesions have been reported. In this paper, we report on one patient with RA that had complications from a demyelinating disorder during TNF-blockade therapy using etanercept at 24 months after initial administration. A 66-year-old Japanese woman was diagnosed with RA in 1959. She received various disease-modifying antirheumatic drugs (DMARDs), but all of these agents were ineffective. She was administered etanercept in June 2005, and stayed well. Twenty-four months after the initial administration of etanercept, she developed palsy of bilateral upper extremities and gait disturbance subacutely, and was then admitted to our institute in August 2007. MRI of her spinal cord revealed a high-intensity lesion from the third through to the seventh cervical (C3-C7) levels. Additionally, T2-weighted MRI images showed disseminated high-intensity lesions in the white matter of brain. She was suspected of having a demyelinating disorder based on these MRI findings. There was no significant finding that pointed to another neurological disorder. High-dose corticosteroid therapy was conducted and was effective for her.