Abstract: Objective: To observe the effects of Ice-Water Swimming on pathological changes in gouty rat model and investigate the regulatory mechanism of P2X7R therein. Methods: Male SD rats were divided into Normal group and Experimental groups, which included Gouty Control group, Ice-Water Swimming group and BBG group. Experimental groups were modeled to hyperuricemia and gouty arthritis by inhibiting uric acid metabolism combined with Coderre method. Ice-Water Swimming group were treated with 5 min of endurance swimming in an ice-water mixture at a depth of about 0.5 m for 0 h and 12 h after modeling by Coderre method, while the BBG group were injected intraperitoneally with BBG solution for 1 time immediately after modeling. Formula to calculate ankle swelling index. The serum uric acid level of rats was detected by uricase assay. The expression level of serum inflammatory factors IL-1β, IL-6 and TNF-α was detected by ELISA. HE staining was used to observe the pathological state of the subject ankle joints. Western Blot and Immunohistochemistry for P2X7R and NLRP3 Protein Expression in Synovial Tissue respectively. Results: Compared with Normal group, the serum uric acid level and ankle joint swelling index of Experimental groups were significantly higher (P < 0.05 or P < 0.01), and the synovial tissues all had different degrees of inflammatory infiltration. Compared with Gouty control group, the ankle swelling index of Ice-Water Swimming group was significantly higher at 12h (P < 0.05). The serum IL-1β, IL-6, TNF-α levels (P < 0.01) and the protein expression of P2X7R, NLRP3 in the synovial tissues were all significantly elevated (P < 0.05). Pathology results showed that the cartilage surface was broken. In addition, the synovial tissue showed severe hyperplasia and erosion, accompanied by a large number of inflammatory cell aggregates. There were no significant changes in P2X7R, NLRP3 protein expression and pathological damage in synovial tissues of BBG group compared with Gouty control group (P > 0.05), whereas the expression of serum IL-1β, IL-6, and TNF-α were all significantly suppressed (P < 0.01). Conclusion: Cold stimulation and strenuous exercise simulated by Ice-Water Swimming can exacerbate pathological damage in gouty arthritis by a mechanism that may be related to high localized P2X7R expression in the joints.