Systemic juvenile idiopathic arthritis (JIA) is a subtype of chronic childhood arthritis of unknown etiology, manifested by long-lasting systemic inflammation and complicated with joint destruction, functional disability, and growth impairment. Macrophage activation syndrome is the most devastating complication, which is associated with serious morbidity. Interleukin (IL)-6 has been thought to be a pathogenic factor of this disease. Anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed, and we investigated the safety and efficacy of tocilizumab in children with this disorder. The Phase II trial revealed that high-grade fever abruptly subsided, and that inflammatory makers were also normalized. The optimal dose of tocilizumab for systemic JIA was revealed 8 mg/kg at 2 weeks interval. The Phase III trial, a placebo-controlled, double-blind study, indicated that patients in tocilizumab group had sustained in clinical measures of effectiveness and wellbeing, whereas most of those in the placebo group needed rescue treatment. The most common adverse events were symptoms of mild infections and transient increases of ALT. Serious adverse events were anaphylactoid reaction, and gastrointestinal hemorrhage. Clinical and laboratory improvement in fever, sickness behavior, CRP gene expression, and chronic inflammatory anemia in children with systemic JIA treated with tocilizumab indicated the possible roles played by IL-6 in this inflammatory disease. Thus, tocilizumab is generally safe and well-tolerated. It might be a suitable treatment in the control of this disorder, which has so far been difficult to manage.