AIM: To investigate the inhibitory effect of Zushima ointment on inflammation and bone destruction in CIA mice. METHODS: SPF grade male DBA/1 mice were used, 6 were randomly selected as the normal group, and 18 CIA mice that were successfully modelled were randomly divided into the model group, the plaster group (1.0 g/kg), and the fuselage group (0.12 g per time) according to the random number table method, 6 mice in each group, and each administered group was given medication according to the body mass, and saline was given to both the normal and model groups. The normal group and the model group were given saline, and breathable adhesive paper was applied once a day for 4 h/session for 4 consecutive weeks. The arthritis scoring index was used to observe the changes of arthritis symptoms and arthritis index scores of mice in each group. Micro-CT was used to observe the damage of hind paw of mice, real-time fluorescence PCR was used to detect the mRNA expression of IL-17, IL-1β and TNF-α in ankle joint tissues, and immunohistochemistry was used to detect the expression of OPG and RANKL proteins in ankle joint tissues, and hematoxylin-eosin (HE) staining was used to observe the pathological changes of synovial tissues after the treatment. The pathological changes of synovial tissue were observed after hematoxylin-eosin (HE) staining, and the changes of osteoclasts in ankle joint tissue were observed by anti-tartaric acid phosphatase (TRAP) method. RESULTS: Compared with the normal group, the arthritis index score of the model mice was significantly higher (P<0.05). Micro-CT showed severe bone erosion in the hind paws of the mice, destruction of the bone surface and reduction of bone volume. The expression of IL-17, IL-1β and TNF-α mRNA (PCR) in the ankle joint tissues was significantly higher (P<0.05). Immunohistochemistry showed that the relative expression of OPG protein in the ankle joint tissues was reduced (P<0.05). Immunohistochemistry showed a decrease in the relative expression of OPG protein (P<0.01) and an increase in the relative expression of RANKL protein (P<0.01). HE results showed moderate inflammatory cell infiltration, swelling of synovial cells, massive formation of vascular opacities and synovial hyperplasia; an increase in the number of osteoclasts, roughness of the surface of articular cartilage tissue, severe bone destruction and thinning of the cartilage layer. Compared with the model group, the arthritic symptoms of mice in the cream group and the futalin group were relieved and the arthritis index score was reduced; the bone density of the mice's hind paws improved, effectively relieving osteoporosis; the expression of IL-17, IL-1β and TNF-α mRNA (PCR) in the ankle joint tissue was significantly reduced (P<0.05); the immunohistochemical results showed that the relative expression of OPG protein was increased (P<0.05), the relative expression of RANKL protein decreased (P<0.01). HE results showed that synovial cell enlargement was significantly improved, mild inflammatory cell infiltration, synovial hyperplasia was not obvious; the number of broken bone was reduced, articular cartilage destruction was significantly improved and relieved, and the thickness of cartilage layer was significantly increased. CONCLUSION: Ancestral hemp poultice relieves local symptoms of RA, reduces the expression of inflammatory factors and attenuates the inflammatory response, possibly by inhibiting osteoclast differentiation and activation through modulation of the OPG/RANKL signalling axis, which further ameliorates the biological effects of articular bone and cartilage destruction.