Matrix metalloproteinases (MMPs) are the family of endopeptidases that primarily catalyze the degradation of the extracellular matrix (ECM), and in turn, increase BBB permeability. MMPs also play critical roles in rheumatoid arthritis (RA), and the expression of specific members of the MMP family, including MMP-3, MMP-8, and MMP-9. However, to the best of our knowledge, there is no combined study that focuses on MMP-9, anti-Cyclic Citrullinated Peptide (anti-CCP), rheumatoid factor immunoglobulin M (RFIgM) and desease activity in RA patients. So, the present study reports the relationship between anti-Cyclic Citrullinated Peptide (anti-CCP), rheumatoid factor immunoglobulin M (RFIgM) and MMP-9, with respect to clinical activity of disease in patients with RA. A total of 85 frozen serum samples, 75 of them belonged to patients with RA, and 10 sample belonged to healthy people (HS), were enrolled prospectively. We used DAS-28 to evaluate disease activity. And then, selected patients were divided into four groups based on their DAS28 scores: remission group (RG), 16 patients (DAS28 < 2.6); low disease activity group (LDAG), 16 patients (DAS28 > 2.6-3.2); moderate disease activity (MDAG), 28 patients (DAS28 > 3.2-5.1); high disease activity group (HDAG), 15 patients (DAS28 > 5.1). The following clinical data gathered from the original patients’ charts. Serum MMP-9 levels and Anti-Cyclic Citrullinated Peptide (anti-CCP) levels were measured using an enzyme linked immunosorbent assay (ELISA; Abbott Diagnostics, USA). Rheumatoid factor (RF) was measured by nephelometry (Beckman Coulter IMMAGE® 800, USA). Our results showed that, patients with RA had significantly higher RF values (P < 0.001) than HS. Anti-CCP levels of RG compared to MDAG were different, but not statistically significant (P = 0.071). Anti-CCP levels were significantly different (P = 0.008) in HS compared to patient groups. Serum levels of MMP-9 in all RA groups were significantly different from HS (P = 0.055). In this regard, MMP-9 and other parameters contribute to pathological condition of RA.