Background: Rheumatoid arthritis (RA) is a systemic disease that causes progressive joint damage and disability.Inflammatory cytokines, including tumor necrosis factor (TNF), and IL-6, which are mainly produced bymacrophages, play a central role in the development of synovitis. For example, TNF play major role in theexpression of adhesion molecules and inflammatory chemokines which, in combination, facilitate increaseinflammatory leukocytes and severe inflammatory responses.In addition to environmental factors, genetic constitution of hosts seems to play a crucial role in acquiring thedisease and its development. The current study was carried out for the detection of any association of HLA-class 11(DR, DQ) with RA disease by genotyping in Iraqi patients, as well as to provide information about genotypes thatmay confer susceptibility or resistance to the development of the disease.Aim of the study: to assess the role, strength and profile of immune response in patients with rheumatoid arthritisby estimation of TNF- α, IL-10 and levels in compare to healthy control group. And to identify any role for certainalleles in exposure to the disease.Material and Method: Five ml of venous blood samples withdrawn from 30 patients suffering from confirmedRheumatoid arthritis disease, 19 patients were females and 11 males in addition to 30 healthy control samples wereenrolled in this study all samples were subjected for (ELISA test) (Enzyme Linked Immunosorbent assay) toestimate the TNF- α, and IL-10 Levels by using the three ml of blood to extract the serum. Another two ml wasused for DNA extraction, and then HLA-Class Il genotyping was performed by polymerase chain reaction-sequencespecific oligonucleotide probes (PCR-SSO).Results: A highly statistically significant variation both in TNF – α levels, and IL-10 between RA patients groupand healthy control group was observed, the P value was <0.001No statically significant differences between males and females in frequency of the RA with0.119 P value.HLA-class II genotyping of RA patients in compare with healthy control reflect significant differences in somealleles. Among DR alleles there were some alleles showed higher frequency in control group; DR*0403 alleleshowed increase frequency in control groups with 35% compared with 6.67% in patients group, and the P value was0.020, which is considered as statistically significant Another DR*701 allele showed increase frequency in patientsgroups with 9 cases 30% and the P value was 0.007. Concerning DQ allele’s genotyping no significant allele’sfrequency was noticed. Although *0202 allele occurred in 40% of patients group and 15% in control groups it wasnot significant statistically as the P value was more than 0.05