OBJECTIVE: To research the effects of Qubi Zhentong Recipe (QZR) on the expressions of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) in the synovial of rats with collagen-inducing arthritis (CIA), and to discuss its mechanisms of action. METHODS: Healthy male Wistar rats were recruited and randomly divided into the model group ( n = 50) and the normal control group (n = 10). Rats of the model group were injected with type II collagen of bovine (BC II) emulsion in the tail and nape to establish the CIA model. After successful modeling, 30 successfully modeled rats were selected and randomly divided into three groups, i.e., the model group (n = 10), the QZR group (n = 10), and the methotrexate (MTX) group (n = 10). Rats in the normal control group and the model group were administered with physiological saline by gastrogavage, while those in the QZR group were administered with QZR at 22.9 g/kg by gastrogavage. All medication was performed once daily. The rats in the MTX group were administered with MTX suspension at 0.78 mg/kg by gastrogavage, once per week. After 30-day treatment, the levels of IL-1beta, IL-8, and VEGF in the synovial were detected by immunohistochemical method. The arthritis index (AI) was scored before and after medication. RESULTS: After treatment the AL score of the QZR group and the MTX group was obviously lower than that of the model group (P < 0.01). The AI score of the two drug groups were lower than that before treatment (P < 0.01). Compared with the normal control group, the expression levels of IL-1beta, IL-8, and VEGF obviously increased in the model group (P < 0.01). Compared with the model group, the expression levels of IL-1beta, IL-8, and VEGF were significantly lower in the two drug groups (P < 0.01). But there was no statistical difference between the QZR group and the MTX group (P > 0.05). CONCLUSION: Decreasing the expression levels of IL-1beta, IL-8, and VEGF in the synovial of CIA rats may be one of the mechanisms for treating CIA by QZR.