Background: Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology. Neuro-Behcet’s disease (NBD) induce serious CNS complications and are known to be the main cause of long-term morbidity and mortality. IL‐37 is a natural suppressor of innate inflammation which its role in NBD has not been fully understood. Objective: To determine the expression of IL-37 in cerebrospinal fluid (CSF) and its relationship with other inflammatory cytokines. Methods: Level of IL-37, IL-6, IL-17, IL-21, TSLP and TGF-β were measured in CSF of 22 patients with NBD and 12 non-inflammatory neurological disease (NIND) and 10 headache attributed to Behçet's disease (HaBD) by enzyme‐linked immunosorbent assay (ELISA). In addition, IL-37 mRNA relative expression was detected by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Results: CSF level and mRNA expression of IL‐37 were elevated in NBD patients compared to those in NIND and HaBD patients. Levels of IL-6, IL-17, IL-21 and TSLP were found to be increased in NBD patients and were inversely associated with IL-37 level. Moreover, TGF-β level in CSF of NBD patients was positively correlated with IL-37 levels. IL-37 increased significantly after treatment and in remission group, but TGF-β was only increased in treatment group. Conclusion: IL‐37 expression increased in NBD patients, and correlated with disease activity. Our data conclude that IL-37 could be a disease marker in NBD, however it requires further studies.