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miRNAs are noncoding RNA that play a critical role as fine regulators of gene expression at the posttranscriptional level within cells in numerous autoimmune diseases. miR-221/222 play a role in cancer by regulating cell proliferation, invasion and apoptosis. However, there have been insufficient studies on their role in rheumatoid arthritis (RA). This work is designed to analyze the miR-221/222 expression patterns in peripheral blood mononuclear cells (PBMCs) of patients with RA in comparison with healthy controls using quantitative RT-PCR, in a group of 30 RA patients and 20 healthy controls. The fold change of miR-221/222 expression in PBMCs was significantly elevated (p < 0.01) in RA patients compared with healthy controls. A positive correlation between expression levels of miR-221 and miR-222 was recorded (r = 0.303; p < 0.05). High miR-221/222 expression levels appeared to be elevated with high activity. miR-222 expression in high activity group of RA patients was significantly increased in relation to moderate (p < 0.01) and low (p < 0.001) activity ones with positive correlation (r = 0.363; p < 0.05) between the progress of disease activity and change in miR-222 expression level. ROC analysis showed a sensitivity of 70% and specificity of 75% for miR-221. In miR-222, the sensitivity of 80% and specificity of 70% were recorded. Our data shed some light on the role of miR-221/222 expression in RA patients, and their great potential value as new novel noninvasive biomarkers for disease detection. Therefore; further investigations are warranted to fully elucidate their role in rheumatoid.