The biological agent tocilizumab, is a humanized, anti-human interleukin-6 receptor antibody. A 72-year-old woman developed cognitive impairment during the Phase III clinical trial of tocilizumab for the treatment of rheumatoid arthritis. MRI demonstrated hyperintense dissemination throughout the white matter on T2WI. An initial diagnosis of possible progressive multifocal leukoencephalopathy was made, but the PCR for JC virus DNA was negative in the CSF. The leukoencephalopathy might have been caused by a mechanism related to tocilizumab itself. It is strongly recommended to perform MRI if a patient develops any cognitive impairment during tocilizumab therapy.