Determination of disease activity in patients with rheumatoid arthritis (RA) has become an important component for RA management. The aim of the present study was to investigate the association between circulating levels of serum amyloid A (SAA) and disease activity in RA patients. The types of disease and the respective number of patients enrolled in the present study were as follows: RA, 88; osteoarthritis (OA), 54; systemic lupus erythematosus (SLE), 43; and other autoimmune diseases, 30, as well as 50 healthy controls (HC). SAA levels were measured using an ELISA assay and western blot analysis was used to detect serum SAA levels. The correlations between SAA levels and disease activity score for 28 joints (DAS28), erythrocyte sedimentation rate (ESR) and C‑reactive protein (CRP), respectively, were evaluated; in addition, the presence and absence of rheumatoid factor (RF) and anti‑cyclic citrullinated peptide antibody (anti‑CCP) were detected in respect to SAA levels. The results of the present study demonstrated that serum levels of SAA in RA patients were significantly increased compared to those of the OA, SLE, others and HC patients (P< 0.05). SAA levels were found to be positively correlated with DAS28, ESR and CRP levels (R2= 0.6174, 0.4422 and 0.3919, respectively). In addition, anti‑CCP was not correlated with DAS28 (R2= 0.0154). Furthermore, increased SAA levels were detected in patients with positive anti‑CCP compared with those in anti‑CCP negative subjects (P< 0.01). In conclusion, the results of the present study provided further evidence for possible roles of SAA in RA, which indicated that it may be a useful biomarker for assessing disease severity and may provide additional information about disease activity.