Some evidence suggests that the pathophysiology of schizophrenia is associated with the abnormal immune system, and cytokines may be important in schizophrenia. Cyclooxygenase-2 (COX-2) inhibitors such as celecoxib reduce the production of proinflammatory cytokines including Th1-like cytokines. Indeed, COX-2 inhibitors rebalance type-1 and type-2 immune response. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of chronic schizophrenia in an eight-week, double-blind and placebo-controlled trial. Eligible participants in this study were 60 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV criteria for schizophrenia. Patients were allocated in a random fashion, 30 to risperidone 6 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 30 to risperidone 6 mg/day plus placebo. Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and celecoxib showed a significant superiority over risperidone alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the celecoxib group over the trial. However, the differences were not significant. The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with chronic schizophrenia and anti-inflammatory therapies should be further investigated.