Objective:To investigate whether serum levels of HP are associated with disease activity and the response of DMARDs therapy in the baseline rheumatoid arthritis (RA) patients. Methods: We selected 67 active RA patients who received no DMARDs in the baseline phase and 27 healthy volunteers. Clinical variables, levels of haptoglobin (HP) messenger RNA (mRNA) in peripheral blood mononuclear cells (PBMCs) and HP serum levels were measured at week 0 and week 12, and then, we analyzed the relationships between them. Results: The serum level of HP of RA patients was significantly higher than that of the healthy controls (P < 0.0001), and positively correlated with the disease activity. After 12 weeks of DMARDs treatment, 55.22% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Disease Activity Score of 28 joints [DAS28] decrease≥1.2) and 29.85% were defined as non-responders. The baseline HP in serum level from non-responders was significantly higher than those in responders (P < 0.01) and remained at high level in non-responders after 12 weeks DMARDs treatment. Conclusion: The mRNA in PBMCs and HP serum levels were significantly increased in RA patients and positively associated with RA disease activity. The HP serum levels of baseline of RA patients are correlated with the 12 weeks DMARDs therapy.