Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblastâlike synoviocytes of RA patients (RAâFLS), in comparison with healthy subjects. MEG3 was also downâregulated evidently in lipopolysaccharide (LPS)âtreated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukinâ23 (ILâ23), which, however were reversed in the lentivirus (containing MEG3âencoding sequences)âtransfected chondrocytes. Upâregulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miRâ141, and miRâ141 was upâregulated in LPSâtreated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miRâ141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. Inâvivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miRâ141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA.