To investigate anti-arthritic activity of Aqueous methanolic extract of Pogostemon quadrifolius (AMEPQ) in Freund’s complete adjuvant (FCA)-induced arthritis in rats. Methods: The AMEPQ was prepared and subjected to acute oral toxicity in mice and tested against FCA induced arthritis in rats. Arthritis assessment was done by measuring – paw volume, joint diameter, pain threshold, thermal hyperalgesia, mechanical nociceptive threshold and body weight. Haematological, serum, biochemical and in vivo anti-oxidant parameters were measured on the last day of the study. Histopathological and radiological analyses of ankle joints were also done. MEPQ was administered at the dose of 100, 200 and 400 mg/kg body weight. Results: MEPQ dose dependently showed anti-arthritic activity which was evident with decrease in paw volume, joint diameter and increase in pain threshold, paw withdrawal latency, mechanical nociceptive threshold and body weight when compared to arthritic control group. AMEPQ (400 and 200 mg/kg) exhibits significant (P < 0.001 and P < 0.01, respectively) anti-arthritic activity by increasing levels of RBC, Hb and by decreasing levels of WBC, platelets and also serum C-reactive protein (CRP) and Rheumatoid factor (RF). The anti-arthritic activity was also confirmed with the altered biochemical parameters (AST, ALT, ALP and total protein level) and anti-oxidant parameters (SOD, MDA and GSH). MEPB (400 and 200 mg/kg) and diclofenac (10 mg/ kg) also inhibited joint destruction (histopathological and radiological analysis). Conclusion: P. quadrifolius may be a potential preventive or therapeutic candidate for the treatment of inflammation and arthritis.