Aim: The present work was designed to examine of the potential anti-inflammatory effect of rosuvastatin (ROSV) and/or Lefleunamide (LFLU) against Complete Freunds Adjuvant (CFA)-induced arthritis in rats. Methods: The mRNA level of perxisome proliferator-activated receptor-alpha (PPAR-a) was determined using Real-time PCR. The levels of NF-B, iNOS, IL-6, TNF-a and SOD activity were measured using ELISA. The swollen paws were measured using caliper. The GSH level was measured using colorimetric assay. The level of malondialdehyde (MDA) was determined using thiobarbituric acid reactive substances assay kit. Results: ROSV induced the expression of PPAR-a that suppresses NF-kB as demonstrated by a strong reduction in NF-kB level in animals treated with ROSV. Also, ROSV administration reduced the levels of the inflammatory mediators IL-6 and TNF-a. In addition, iNOS and MDA content as well as expression of MMP-9 and MMP-2 induced by CFA is abrogated in animals treated with ROSV. Also GSH content and SOD activity were highly increased in ROSV-treated animals. Furthermore, the size of right paw induced by CFA was reduced in ROSV-treated rats. Moreover, the histopathological alterations induced by CFA were highly improved in animals treated with ROSV. Similar results were also found in animals treated with LFLU. Importantly, similar effects were obtained in rats treated with both ROSV and LFLU in half doses. Conclusion: This study demonstrates that ROSV as well as LFLU has the ability to inhibit rheumatoid arthritis in experimental model induced by CFA. Importantly, concomitant administration of ROSV and LFLU in half doses synergize against rheumatoid arthritis.