Objective To verify the safety of a newly-developed helium-oxygen diving decompression table in a swine model and preliminarily explore a method for evaluating the safety of decompression profiles based on animal experimental results. Methods Simulated diving was performed in a purpose-built pressurized chamber for large animals. The diving profiles were verified every 6 m at regular operation depth and every 9 m at training and exceptional exposure depth by systematic stratified sampling according to the newly-developed helium-oxygen diving decompression table, and each profile was verified 4-6 times. The animal conditions during simulated diving and symptoms of decompression sickness (DCS) and bubbles flowing through the heart after depression were observed. Blood indicators related to endothelial injury, inflammatory response and oxidative stress levels were assessed. Results No symptoms of oxygen toxicity or DCS, or circulating bubbles were found in the animals exposed with all the 14 tested profiles. The inflammatory response indexes (interleukin 1β, tumor necrosis factor α), endothelial injury indexes (intercellular adhesion molecule 1, vascular cell adhesion molecule 1) and oxidative stress index (H₂O₂) were compared before simulated diving and immediately (0 h), 6 h and 24 h after decompression, and there were no significant differences (all P＞0.05). Conclusion As far as the swine model is concerned, the newly-developed helium-oxygen diving decompression table has excellent safety. More data are needed to verify the preliminary experimental method for evaluating the safety of diving decompression table.