Abstract: This study investigated the effect of morin, an active ingredient of the family Moraceae, on collagen-induced arthritis (CIA) in mice, and explored the underlying mechanism from the perspective of recovering immune balance. The collagen was used to induce model of CIA in mice, morin was administered by gavage, and arthritis index (AI) score, imaging and histopathological changes of the paws and ankle joints, and the levels of proinflammatory factors, proinflammatory mediators as well as the IgG class antibodies in serum were detected. In addition, the frequencies of T helper 17 (Th17) and regulatory T (Treg) cells and the levels of relevant transcription factors and functional factors in lymph nodes/spleen as well as the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. The results showed that oral administration of morin significantly reduced the AI score, improved joint swelling and bone damage, reduced the pathological score, and down-regulated the levels of proinflammatory factorstumor necrosis factor-‍α (TNF-‍α), IL-6 and IL-1β, proinflammatory mediatorsprostaglandin E₂ (PGE₂), matrix metalloproteinase-13 (MMP-13) and nitric oxide (NO) and IgG class antibodies (IgG and IgG2a) in serum. Moreover, the percentage of Th17 cells, the expressions of Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factors IL-17A, IL-21 and IL-22 in lymph nodes/spleen, as well as the level of IL-17A in serum were down-regulated, while the percentage of Treg cells, the expressions of Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factors IL-10 and transforming growth factor-‍β (TGF-‍β) in lymph nodes/spleen, as well as the level of IL-10 in serum were up-regulated. All animal treatments were approved by the Animal Ethics Committee of China Pharmaceutical University and strictly followed the welfare regulations of laboratory animals of China Pharmaceutical University. This study indicates the therapeutic effect of morin on mice with CIA, and the mechanism is associated with the improvement of Th17/Treg imbalance, which provides a theoretical basis for the clinical application of morin.