Objective. Interleukin 34 ( IL-34) and microRNA 21 ( miR-21) were found to be involved in the pathological process of rheumatoid arthritis ( RA), but the details were unclear. In this study, we aimed to clarify the relationship between IL-34 and miR-21 in RA. Methods. IL-34 concentrations in serum and synovial fluid ( SF) of patients with RA were measured by ELISA. Fibroblast-like synovial cells ( FLS) were cultured for evaluation of STAT3 activation, miR-21, and Bax/Bcl-2 expression by Western blot and real-time PCR. Correlations were analyzed between clinical features and detectable variables including SF IL-34 levels and miR-21 expression. Results. SF IL-34 levels were significantly higher in patients with RA who had a high 28-joint Disease Activity Score ( DAS28 >= 3.2) than in those with a lower DAS28 ( DAS28 < 3.2). DAS28 scores and miR-21 expression in FLS had a significant positive correlation with the SF IL-34 levels. In addition, IL-34 stimulation strengthened the activation of p-STAT3, resulting in the increment of miR-21 expression. Inhibiting of miR-21 expression contributed to decreased Bcl-2/Bax ratio, suggesting that miR-21 was involved in the resistance to apoptosis. With the blocking of the colony-stimulating factor-1 receptor ( CSF1R), decreased protein expressions including CSF1R, p-STAT3/STAT3, and Bcl-2/Bax were shown, suggesting that CSF1R participated in the biological functions of IL-34 in RA. Conclusion. The IL-34/STAT3/miR-21 pathway is crucial for the survival of synovial fibroblasts in RA, which might be candidate therapeutic targets for RA treatment.