This study aimed to evaluate the role of Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody in comparison to Cartilage oligomeric matrix protein (COMP) in Rheumatoid Arthritis (RA) patients as predictors of the disease activity and cartilage destruction. Thestudy included 60 patients &10 apparently healthy subjects .They were divided into 4 groups. Group I: consisted of 20 patients with established rheumatoid arthritis( and positiverheumatoid factor)Group 2: 20 suspected (rheumatoid factor negative)patients Group 3:20 patients with other autoimmune inflammatory diseases (15 with psoaritic arthritis, 5 with systemic lupus erthromatosis).andGroup 4: 10 age and sexmatched controls. For each patient medical examination and disease activity evaluation using Disease Activity Score (DAS) was performed Anti cyclic citrullinated peptide (anti CCP)levelwasmeasuredby ELISA method and cartilage oligomeric matrix protein (COMP)wasdetermined by indirect immune fluorescent method.Serum level of anti CCP antibodies and COMP were Significantly related to DAS (disease activity score) and cartilage destruction, the serum presence of COMP was highly significant in rheumatoid arthritis patients than those with other autoimmune disease ,the sensitivity of anti CCP in diagnosis of RA was 77.5 % and specificity was96.6%It is concluded that anti CCP, and COMP may be a useful noninvasive markers for disease activity and cartilage destruction.