The present study evaluated the anti-inflammatory activity of fangchinoline in rheumatoid arthritis-induced rats. Rats were grouped into sham (group I), rheumatoid arthritis (group II, control), fangchinoline (2 μM, group III), and fangchinoline (4 μM, group IV) groups. The serum levels of lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), prostaglandin-E2 (PGE₂), nitric oxide (NO), zinc, ceruloplasmin, uric acid, and copper were determined. Chondrocyte cell proliferation, reactive oxygen species (ROS), and cellular levels of TNF-α and IL-6 were assessed. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels by fangchinoline treatment. Fangchinoline treatment significantly reduced the TNF-α level by 17.8% and 40.8% in groups III and IV respectively, whereas IL-6 was significantly decreased by 23.2% and 45%, respectively. Fangchinoline treatment significantly decreased the MMP-3 level by 23.1% and 65.1% in groups III and IV respectively, whereas PGE₂ was significantly decreased by 31.8% and 63.8%, respectively. Fangchinoline treatment decreased NO, uric acid, ceruloplasmin, and copper levels, whereas the zinc content was increased. Chondrocyte proliferation was significantly reduced to 73.3%, 51.3%, and 42.4% at 2 μM, 4 μM, and 6 μM fangchinoline treatment respectively. Intracellular ROS, TNF-α, and IL-6 levels were significantly reduced in the chondrocytes. Protein expression of TNF-α was significantly decreased by 0.27-, 0.53-, and 0.67-fold at 2 μM, 4 μM, and 6 μM fangchinoline treatment respectively. In conclusion, fangchinoline is effective as an anti-inflammatory agent in rheumatoid arthritis-induced rats.