To investigate the effect of miR-21 on the proliferation and apoptosis of rheumatoid arthritis (RA) fibrolast like synoviocytes (FLS). Methods Realtime PCR method was used to detect the difference of miR-21 expression between normal and RA-FLS. RA-FLS were divided into Control, miR-NC (transfection mimics control), miR-21 (transfection miR-21 mimics), miR-21+IGF-1 group (transfection miR-21 mimics, PI3K/Akt signaling pathway specific treatment with PI3K/Akt activator IGF-1), CCK-8 experiment to analyze changes in cell proliferation activity, flow cytometry to analyze changes in cell apoptosis, Western blot analysis of C-Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt and p-Akt proteins. Results Compared with normal-FLS, the expression level of miR-21 in RA-FLS decreased (P＜0.05). Compared with the Control and miR-NC groups, the miR-21 expression level in the RA-FLS cells of the miR-21 group increased, the cell proliferation activity decreased, the apoptosis rate increased, and the expression of C-Caspase-3 and Bax proteins in the cells increased, the expression of Bcl-2 protein decreased, and the protein levels of p-PI3K/PI3K and p-Akt/Akt decreased (P＜0.05). Compared with the miR-21 group, the proliferation activity of RA-FLS in the miR-21+IGF-1 group was increased, the apoptosis rate was decreased, the expression of p-PI3K/PI3K, p-Akt/Akt protein in the cells increased, and C-Caspase-3,Bax protein decreased, and the expression of Bcl-2 protein increased (P＜0.05). Conclusion Up regulation of miR-21 can inhibit the proliferation of RA-FLS and induce cell apoptosis, the mechanism is related to the reduction of PI3K/Akt signal activation level.