Objective: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid isolated from Apocyanaceae plants. This study was designed to investigate the effects of ellipticine on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA).Methods: RA-FLSs were exposed to different concentrations of ellipticine (i.e., 0.5, 1, 2, 4 and 8 μM) for 24–72h and measured for viability, proliferation and apoptosis. The involvement of signal transducer and activators of transcription 3 (STAT3) signaling in the action of ellipticine was determined by Western blot analysis, luciferase reporter assay and rescue experiments.Results: Ellipticine treatment significantly inhibited the viability and proliferation of RA-FLSs in a concentration-dependent manner. In contrast, ellipticine exposure did not alter the viability of normal human FLSs. Moreover, ellipticine triggered significant apoptosis and increased caspase-3 activity in RA-FLSs. Mechanistically, ellipticine reduced the phosphorylation of STAT3 and downregulated the expression of Mcl-1, cyclin D1 and Bcl-2. Luciferase reporter assay demonstrated that ellipticine treatment led to a significant inhibition of STAT3-mediated transcriptional activity in RA-FLSs. Overexpression of constitutively active STAT3 reversed the suppressive effects of ellipticine on RA-FLSs, which was accompanied by restoration of Mcl-1, cyclin D1 and Bcl-2.Discussion and conclusions: Ellipticine shows anti-proliferative and pro-apoptotic effects on RA-FLSs through inhibition of the STAT3 pathway and may have therapeutic potential in RA.