Quercetin (QU) has been shown obvious anti-arthritic property in pre-clinical studies or clinical studies. Howbeit, the underlying mechanism of it is still not revealed distinctly and should be gotten further insight into. QU at a dosage of 150 mg/kg was administered orally in collagen-induced arthritis rats and then the clinical symptoms were monitored. The protein levels of Th17/Treg-related cytokines were determined by ELISA, and the mRNA levels of cytokines and transcription factors associated with the Th17 and Treg phenotypes were evaluated by real-time PCR, the proportions of Th17 and Treg cells were assessed by flow cytometry. The results showed that QU administration yielded an obvious mitigation of arthritic manifestations including high arthritic scores and paw edema, which was accompanied with decrement of Th17-related cytokines (IL-17A and IL-21) and increment of Treg-related cytokines (IL-10 and TGF-β). QU decreased the percentage of Th17 cells, while increased the percentage of Treg cells. In addition, the activation of NLRP3 inflammasome which plays a crucial role in the development of RA was determined and found that the protein expressions of NLRP3, Caspase-1 and IL-1β were diminished by QU significantly. Moreover, the protein levels of inflammatory mediators which were recognized as chief culprits in inflammatory reaction were assayed. The contents of inflammatory mediators inclusive of TNF-α, IL-1β, IL-6, PGE2, COX-2 and iNOS were down-regulated markedly by QU. But the inhibitory effect of QU on inflammatory mediators was nearly abolished by Heme Oxygenase 1 (HO-1) siRNA. Taken together, QU attenuates CIA via modulating the Th17/Treg balance, inhibiting NLRP3 inflammasome activation as well as activating HO-1-mediated anti-inflammatory response.