Objective: To compare and study the acute high-altitude model established by SD rats under two types of hypoxic stress modes: high-altitude field and simulated high-altitude environment. Methods: SD rats were rapidly entered into a simulated high-altitude animal experimental chamber (4000 m) or a high-altitude field laboratory (4010 m) to establish a rat rapid high-altitude model. After 24 or 72 hours of exposure, physiological and pathological indicators related to high-altitude changes were collected and measured, mainly including blood routine, blood biochemistry, blood gas, oxidative damage indicators, inflammation indicators, and pathological tissue analysis. Finally, differential analysis was conducted on the results to obtain a differential evaluation report. Results：At the same altitude, both high-altitude field and simulated high-altitude exposure for 72 hours can cause significant lung and brain damage. Under the same exposure time, the blood routine, blood biochemistry, and blood gas results of animal bodies are similar. There was no significant difference in the detection results of inflammation indicators（IL-6, IL-1β, MCP-1 and IFN-γ）and oxidative damage indicators (MDA, SOD, and GSH). However, the PCO2 and BE of the simulated 72-hour group were significantly higher than those of other treatment groups, and the high-altitude field brain coefficient was significantly higher than that of the simulated high-altitude group. These results suggest that there may be slight differences between high-altitude field and simulated high-altitude environments. Conclusion: The simulated high-altitude animal experimental chamber can successfully establish a rapid high-altitude animal model. The simulated altitude can be appropriately increased on the basis of 4000 meters. If an altitude of 4000 meters is used, the exposure time should be greater than 24 hours but slightly shorter than 72 hours. If conditions permit, it is advisable to go to the plateau for on-site experiments as much as possible.