Abstract Background: Chitotriosidase and YKL-40 are well-known in humans as Glyco_18 domain-containing proteins that are the common feature of mammalian chitinases and chitinaselike proteins. Previously, increased levels of YKL-40 were found correlated with the disease activity of rheumatoid arthritis. However, serum chitotriosidase activity in rheumatoid arthritis is not known yet. The aim of this study was to determine YKL-40 and chitotriosidase in patients with rheu - matoid arthritis and to compare these markers with traditi - onal ones such as C-reactive protein and erythrocyte sedimentation rate. Methods: Chitotriosidase, YKL-40 and C-reactive protein were measured in serum samples from 27 patients with rheumatoid arthritis and 27 healthy people. Chitotriosidase, YKL-40, C-reactive protein, and erythrocyte sedimentation rate were determined by a fluorometer, ELISA, nephelometer, and Western Green method, respectively. Results: Serum chitotriosidase activities and YKL-40 levels were higher in rheumatoid arthritis group than in control. A significant positive correlation was found between chitotriosidase and YKL-40. In ROC analysis, the areas under curves for chitotriosidase, C-reactive protein, erythrocyte sedimentation rate, and YKL-40 were 0.96, 0.84, 0.76, and 0.65, respectively. Area under the curve for chitotriosidase was significantly higher than the area for erythrocyte sedimentation rate (p=0.005) and for YKL-40 (p=0.0001), but not for Creactive protein (p=0.055). Conclusions: Serum chitotriosidase was significantly in creas - ed in patients with rheumatoid arthritis. Among all the param - eters evaluated, chitotriosidase was the most sensitive and specific one. Comprehensive studies covering larger populations are needed to elucidate the relationship bet ween chitinases, in particular chitotriosidase and rheumatoid arthritis.