AIM: To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuricaemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway. METHODS: Forty-eight SD male rats were randomly divided into blank, model, and colchicine groups (0.3 mg·kg-1·d-1), and Origre sanzhou decotion low, medium and highdosage groups (7.42, 14.85, 29.70 g·kg-1·d-1), which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxalate, which was used for the treatment of acute gouty arthritis combined with hyperuricemia. A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia, combined with the modified Coderre method. After 7 days of intervention, the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated, the blood uric acid (HUA) level of rats was determined by biochemical method, the histopathological and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining, and the serum levels of inflammatory factors, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β were determined by enzyme-linked immunosorbent assay (ELISA), and Western blotting was performed to determine the levels of inflammatory factors, TNF-α, and IL-1β. The protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), and nuclear factor-κB (NF-κB) in the synovial tissues of the ankle joints of the rats were determined by Western blot method, and the mRNA expression of TLR4, Myd88, and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). RESULTS: Compared with the blank group, rats in the model group showed significantly lower ankle joint swelling (P<0.01), increased levels of HUA, disorganised synovial tissue structure, large number of inflammatory cells infiltration, and significantly higher serum levels of TNF-α, IL-6, and IL-1β (P<0.01), and the protein and mRNA expression levels of TLR4, Myd88, and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased (P<0.01). levels were significantly increased (P<0.01); compared with the model group, joint swelling was significantly reduced in the colchicine group, and the medium- and high-dose groups of Qingre sanzhuo decoction (P<0.05); synovial hyperplasia and inflammatory cell infiltration were improved in the colchicine group and the medium- and high-dose groups of Qingre sanzhuo decoction, and the HUA and the levels of TNF-α, IL-6, and IL-1β were significantly decreased in the dosing groups (P<0.05, P<0.01), and compared with the model group, the medium- and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4, Myd88, and NF-κB protein and mRNA (P<0.01). CONCLUSION: Qingre sanzhuo decoction reduces the release of inflammatory factors by inhibiting the TLR4/Myd88/NF-κB pathway, and plays a role in the treatment of hyperuricaemia combined with gouty arthritis.