Objective: To investigate the mechanism of gout attack in hyperuricemic rats under ice-water swimming conditions based on P2X7R. Methods: Male SD rats were randomly divided into control group, high-purine diet + ice-water swimming group, high-purine diet group, and ice-water swimming group. Hyperuricemia was induced by gavage with potassium oxonate combined with yeast. Ice-water swimming was performed by 5-minute endurance swimming in an ice-water mixture. The experiment lasted for 21 days. During the experiment, changes in the diameter of the right ankle joint and foot thickness were measured every two days to calculate the swelling index; serum uric acid levels in rats were detected by the uricase method; serum and liver xanthine oxidase (XOD) levels were detected by colorimetric method; serum ATP levels were detected by phosphomolybdic acid colorimetric method; uric acid crystals in joint fluid were observed by polarized light microscopy; serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA); venous blood neutrophil count was detected by an automated hematology analyzer; pathological changes in ankle joint and synovial tissue were observed by HE staining; and P2X7R and NLRP3 protein expression in synovial tissue were detected by Western blot and immunohistochemistry, respectively. Results: Compared with the control group, serum uric acid levels in the high-purine diet + ice-water swimming group were significantly increased (P<0.01), and significantly higher than those in the high-purine diet group and ice-water swimming group (P<0.01 or P<0.05). Serum and liver XOD levels were significantly increased (P<0.01). The swelling index of the right ankle joint and foot thickness in the high-purine diet + ice-water swimming group was significantly increased, reaching a peak swelling on day 13 (P<0.01 or P<0.05), and inflammatory infiltration was observed in the synovial tissue. Venous blood neutrophil count was significantly increased (P<0.01), and serum inflammatory factors IL-1β, IL-6, and TNF-α levels were significantly increased (P<0.01). Serum ATP levels in the high-purine diet + ice-water swimming group showed a decreasing trend (P<0.1). Uric acid crystals were observed in joint fluid smears. P2X7R and NLRP3 protein expression in synovial tissue were significantly increased (P<0.01 or P<0.05). Conclusion: Ice-water swimming under hyperuricemic conditions can lead to ATP metabolic imbalance, promote increased uric acid levels and urate deposition, activate P2X7R, and consequently lead to gouty arthritis attack through the ATP-P2X7R-NLRP3 pathway.