Objective To develop a mouse cerebral edema / pulmonary edema model under different conditions and compare method of calculating water content. Methods Fifty male BALB/ c mice were divided randomly into a Control group and four experimental groups: 6000 m/ 48 hours, 6000 m/ 72 hours, 8000 m/ 48 hours,and 8000 m/ 72 hours (n= 10 mice per group). The baseline mass was recorded in each group. Mice in all groups except the Control group were placed in a simulated plateau environment at an altitude of 6000 or 8000 m for 48 or 72 hours. After exposure, the body mass was measured, and the lung wet weight, brain wet weight, lung dry weight, and brain stem weight were determined. Three different method were used to calculate the model water content, and pathological changes in the brain and lung were observed by hematoxylin / eosin staining. ResultsThe body mass decreased significantly in all groups except the control group (P<0. 01), with the greatest decrease after 72 hours at the same altitude. In the pulmonary edema model, pathological analysis showed slight pulmonary edema in the 6000m/ 48 hour group, but there was no significant difference from the control group (P>0. 05). Using the calculation result from method 2 or 3, the water contents were significantly higher in the 6000 m/ 72 hour, 8000 m/ 48 hour, and 8000 m/ 72 hour groups, compared with the Control group (P<0. 01), and pathological analysis indicated significant edema in the lungs in these three groups; however, method 1 found no significant difference in lung water contents in these three groups compared with the control group (P>0. 05). In terms of cerebral edema, method 1 showed that the brain water content in each experimental group was significantly lower than that of the Control group (P<0. 01), while method 2 and 3 showed consistent results, with significantly higher brain water contents in all the experimental groups compared with the Control group ( P<0. 01). Pathological analysis showed significant cerebral edema in all four experimental groups. Conclusions Method 1 is less reliable for calculating water contents, while method 2 and 3 showed similar results, including the ability to correct body mass changes. These method are thus recommended as the standard calculation method for the plateau cerebral edema / pulmonary edema model.