To detect the levels of serum peptidylarginine deiminase (PADI)4 and explore its significance in rheumatoid arthritis (RA).The presence of PADI4, anti-PADI4 antibodies and anti-cyclic citrullinated peptide (CCP) antibodies levels were examined by enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 100 patients with RA, 23 patients with other rheumatic diseases, and 24 healthy controls. The associations between PADI4 and the disease activity score using 28 joint counts (DAS28) score, anti-CCP antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PADI4-94 (rs 2240340) and PADI-104 (rs 1748033) gene polymorphisms and other indexes were analyzed in RA.The levels of PADI4 in RA patients were significantly higher than in other rheumatic diseases and healthy controls (F = 8.75, P < 0.001). There was no significantly difference in levels of PADI4 among ADI4-94 (rs 2240340)/PADI-104 (rs 1748033) genotypes.PADI4 is associated with disease activity involved in the RA pathogenesis and may be a RA pathogenic antigen.