Ｏｂｊｅｃｔｉｖｅ　To investigate the effects and mechanisms of the heat shock protein（HSP） 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin（17-DMAG） on mechanical ventilation-induced lung injury.　Methods　Twenty-eight Male ICR mice（7-9 weeks old） were randomly divided into four groups by random number table method（n=7）：control group（CON group）， mechanical ventilation group（VEN group），17-DMAG group and 17-DMAG + Mechanical ventilation group（17-DMAG+VEN group）. The protein concentration and cell counts of bronchoalveolar lavage fluid were detected after four hours of ventilation. The wet- to-dry weight ratio（W/D） and pathological changes of lung tissue were examined. Interleukin（IL）-1β， tumor necrosis factor-α（TNF-α） and high mobility group box 1（HMGB1） levels in lung tissue homogenates were measured by enzyme-linked immunosorbent assay（ELISA）. 　Results　Protein concentration and cell count from bronchoalveolar lavage fluid in VEN group were （0.29±0.05） g/L and （2.84±0.55）/ml， significantly higher（P<0.01） than those in both CON groups and 17-DMAG+VEN group（P<0.01）. Lung tissue W/D in VEN group was（5.14±0.19） much higher than that in both control group（4.65±0.15） and 17-DMAG+VEN group （4.79±0.14）（P<0.01）. Pre-treatment with 17-DMAG could significantly reduce the ventilation-induced lung tissue damage. Four hours of mechanical ventilation could induce IL-1β， TNF-α and HMGB1 protein expression in lung tissue. Pre-treatment with 17-DMAG could significantly reduce the mechanical ventilation-induced HMGB1 expression： there was statistical difference between 17-DMAG+VEN group（15.4±3.0） mg/g and VEN group（18.9±2.5） mg/g in HMGB1（P<0.05）.　Conclusions　Our results indicate that 17-DMAG can reduce pulmonary edema and exert protective effects in mechanical ventilation-induced lung injury by inhibiting the protein expression of HMGB1.