OBJECTIVE The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA). METHODS Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative. RESULTS Serum CRT levels in RA patients (4.817 ± 2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574 ± 0.942 ng/ml), SLE (4.013 ± 1.536 ng/ml), other autoimmune diseases (3.882 ± 0.837 ng/ml) and HC (3.726 ± 0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P < 0.01). CONCLUSIONS Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.