Objective A comparative study was conducted on rapid high-altitude models established in SD rats under two hypoxic stress modes, namely, a high-altitude field and simulated high-altitude environment, to evaluate the reliability of the simulated high-altitude test chamber. Methods SD rats were placed in a simulated rapid high-altitude animal experimental chamber (4000 m) or rapid high-altitude field laboratory (4010 m) to establish a rapid high-altitude rat model. After 24 or 72 h of exposure, physiological and pathological indicators related to high-altitude changes were collected and measured, mainly routine blood parameters, blood biochemistry, blood gas, oxidative damage indicators ( superoxide dismutase ( SOD), malondialdehyde ( MDA), glutathione peroxidase ( GSH-Px )), and inflammation indicators (interleukin 1β (IL-1β), interferon-γ ( IFN-γ), monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6)), and pathological tissue analysis and hypoxia sensitive gene (hypoxia inducible factor-1α (Hif-1α) and vascular endothelial growth factor A (Vegfa)) testing were performed. Finally, differential analysis was conducted on the result to obtain a differential evaluation report. Results At the same altitude, both high-altitude field and simulated high-altitude exposure for 72 h caused significant lung and brain damage. Under the same exposure time, the routine blood parameter,blood biochemistry, and blood gas result for the rats were similar. There were no significant differences in the detection of inflammation indicators (IL-6, IL-1β, MCP-1, and IFN-γ), oxidative damage indicators (MDA, SOD, and GSH), or hypoxia-sensitive gene expression (Hif-1α and Vegfa) in the brain. However, partial pressure of carbon dioxide (PaCO₂ ) and base excess (BE) were significantly higher in the simulated-72 h group than the other treatment group. The lung hypoxia-sensitive genes (Hif-1α and Vegfa) in the simulated-72 h group showed no significant expression difference with control group, and the brain coefficient of the high-altitude field treatment group was significantly higher than that of the simulated high-altitude treatment group. These result indicate that there may be slight differences between models prepared in high-altitude field and simulated high-altitude environments. Conclusions 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 m. If an altitude of 4000 meters is used, the exposure time should be greater than 24 h but slightly shorter than 72 h. The simulated high-altitude experimental module has good reliability, but it is advisable to use plateaus for on-site experiments as much as possible, if conditions permit.