OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica（Abbreviated as HSH） on rheumatoid arthritis （RA） based on cluster of differentiation 4/lymphocyte cell-specific protein- tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17（CD4/LCK/ZAP70/IL-17） signaling pathway. METHODS The rats were divided into normal group， model group， HSH low-dose， medium-dose and high-dose groups （2.7， 10.8， 21.6 mg/kg） and positive control group （Tripterygium glycosides tablet， 6.3 mg/kg）， with 10 rats in each group. Except for normal group， RA rat model was induced by complete Freund’s adjuvant in other groups. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 28 consecutive days. The changes in ankle joint swelling and arthritis index in rats were determined； the pathological changes of ankle joint tissue were observed； the levels of inflammatory factors [IL-1β， IL-21， IL-17A， IL-2， interferon-γ （IFN-γ） and IL-6] in serum and joint fluid of rats were determined； the levels of Th1， Th17 and Treg cells in the whole blood and spleen of rats were detected； protein and mRNA expressions of LCK， proto-oncogene tyrosine-protein kinase Fyn （Fyn）， ZAP70， CD45， RAR-related orphan receptor γt （RORγt）， and forkhead box protein 3 （Foxp3） in ankle synovial tissue were determined. RESULTS Compared with normal group， the changes in ankle joint swelling， arthritis index， the levels of IL-1β， IL-21， IL-17A， IL-2， IFN-γ and IL-6 in serum and joint fluid， the levels of Th1， Th17 cells and Th17/Treg value in whole blood and spleen， and the protein and mRNA expression levels of LCK， Fyn， ZAP70， CD45， and RORγt in ankle joint synovium were all significantly increased/elevated （P＜0.05）. The level of Treg cells in the spleen， as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased （P＜0.05）. Compared with model group， most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH （P＜0.05）. The degree of pathological changes in ankle joint tissues was markedly improved， and inflammation was alleviated. CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway， thereby modulating the Th17/Treg balance. This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.