Ginkgo biloba reduces the severity of acute mountain sickness in humans, but protection against high altitude pulmonary edema (HAPE) has not been reported. This study was conducted to determine if G. biloba would prevent early HAPE in rats. Six rats (ginkgo group) received G. biloba (200 mg/kg body weight in drinking water and an equal amount in peanut butter) for 2 days before and during high altitude exposure (380 mmHg pressure for 24 h). Six other rats (control group) received water and peanut butter alone. Protein concentrations in bronchoalveolar lavage fluid (BALF) were increased in control rats (19.8 +/- 2.6 mg/dL) compared to ginkgo rats (11.6 +/- 0.9 mg/dL; p = 0.014), demonstrating that untreated (control) rats developed mild HAPE following high altitude exposure. For comparison, BALF protein concentrations in sea-level rats (air group) given peanut butter were 12.6 +/- 0.8 mg/dL (n = 6). Although pleural effusions did not develop in any rats, the protein concentrations of pleural fluid were also increased in control rats (4.9 +/- 0.16 g/dL) compared to ginkgo rats (4.0 +/- 0.13; p = 0.001); air group: 3.5 +/- 0.08 g/dL. There were no differences in wet/dry lung weight ratios between groups, but wet left lung weights/preexposure body weight were increased in control rats (1.26 +/- 0.02 g/kg) compared to the ginkgo group (1.17 +/- 0.01 g/kg; p = 0.002); air group: 1.11 +/- 0.03 g/kg. In conclusion, the data show that G. biloba prevents the development of early HAPE in rats.