Objective To observe the effects of ice-water swimming on pathological changes in model gouty rats, and investigate the relevant regulatory mechanism of the purinergic P2X7R receptor. Methods Male Sprague Dawley rats were divided into normal(NORM) and experimental groups including gouty control(GC), ice-water swimming(IWS), and Brilliant Blue G (BBG, a P2X7R inhibitor) groups. Rats in the experimental groups were modeled to simulate hyperuricemia and gouty arthritis by inhibiting uric acid metabolism combined with the Coderre method. Rats in the 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 the Coderre method, while rats in the BBG group were injected intraperitoneally with BBG solution once after modeling. Ankle swelling index was calculated using a formula. Serum uric acid levels were detected by uricase assay, and serum levels of the inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-αwere detected by enzyme-linked immunosorbent assay. The pathological status of the ankle joints was examined by hematoxylin and eosin staining. P2X7R and NLRP3 protein expression levels in synovial tissue were detected by Western blot and immunohistochemistry, respectively. Results Serum uric acid levels and the ankle joint swelling index were significantly higher in the experimental groups compared with the normal group (P<0.05 or P<0.01), and the synovial tissues showed different degrees of inflammatory infiltration. The ankle swelling index was significantly higher in the ice water swimming group compared with the gouty control group at 12h (P<0.05). Serum IL-1β, IL-6, and TNF-α levels (P<0.01) and P2X7R and NLRP3 protein levels in synovial tissues were all significantly elevated (P<0.05). Histopathology showed that the cartilage surface was broken and the synovial tissue showed severe hyperplasia and erosion, accompanied by numerous inflammatory cell aggregates. There were no significant changes in P2X7R or NLRP3 protein expression or pathology in synovial tissues in the BBG group compared with the gouty control group (P>0.05), but serum IL-1β, IL-6, and TNF-α levels were all significantly suppressed (P<0.01). Conclusions Cold stimulation and strenuous exercise simulated by ice-water swimming may exacerbate pathological damage in gouty arthritis via a mechanism related to high P2X7R expression in the joints.