Demethoxycurcumin (DMC) is one of the main bioactive and stable constituent from the mixture of polyphenols, collectively referred as curcuminoids. The study aimed to investigate the anti-arthritic potential and possible mechanism of DMC in Freund’s complete adjuvant (FCA) arthritis rat model. Rat paw edema, body weight changes, alterations in hematological (Hb, RBC, WBC and ESR) and biochemical parameters were observed. ELISA analysis was performed to detect serum TNF-⍺, IL-1β, IL-6 and IL-10 followed by real-time RT-PCR for determining pro/anti-inflammatory markers in synovium tissue. DMC (60mg/kg b.w.) significantly ameliorated paw swelling and regained the body weight loss. Also DMC treatment brought back the altered hematological and biochemical parameters comparable to non-immunized rats. DMC administration remarkably suppressed the overproduction and mRNA expression of TNF-⍺, IL-1β and IL-6 in contrast to IL-10, which was markedly increased by DMC treatment. Dramatic inhibition of histopathological and radiological changes caused by FCA injection was observed in DMC treated group. Taken together, the study demonstrates that DMC is an effective anti-arthritic fraction from the group of curcuminoids responsible for the anti-inflammatory and reparative effects, which could be mediated via decrease in mRNA expression of TNF-⍺, IL-1β and IL-6 and increase of IL-10.