Rheumatoid arthritis (RA) is a chronic autoimmune disease with a heterogeneous clinical presentation. Initially manifested locally, RA later develops into a systemic disease that involves major organ systems and reduces life expectancy. RA is a common cause of permanent disability, characterized by chronic inflammation of the synovial tissues and ultimately cartilage and bone destruction. Thus, attention should be given to the identification of poor prognostic indicator parameters, because ideally the definition of therapeutic intensity level should be based on reliable severity predictors. Hypoxia is necessary for the development of rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), due to enhanced infiltration of immune cells. Additionally, hypoxia induces transcription factors formation; hypoxia inducible factor HIFs, which trigger up-regulation of pro-angiogenic factors and mediators involved in glycolysis. The HIF pathway allows cells to survive during hypoxic conditions and plays a major role in RA disease progression, whereas especially HIF-1α acts as a key regulator of inflammation. Hypoxia-inducible factor (HIF)-1, the oxygen-sensitive transcription factor that allows adaptation to a hypoxic environment. Anti-Cyclic Citrullinated Peptide (Anti-CCP) are autoantibodies against citrullinated peptide and proteins. During inflammation arginine residues present in some protein get converted into citrulline residue, a process called citrullination. The synovium in RA contains many citrullinated proteins. The aim of the work was to estimate the amounts of Hypoxia-inducible factor alpha (HIA) and Anti-CCP in the serum of Rheumatoid Arthritis patients with variable disease activity and to study the relation between HIA and Anti-CCP in rheumatoid arthritis