Objective To investigate the effect of acute irradiation by high power millimeter wave on the pathological changes of mouse lung tissue. Methods The BALB/c mice were vertically placed under the high power millimeter wave equipment with working frequency of 34. 1 GHz, and the mean output power were 5,10 and 12 W while the distance between the animal and the bottom of the irradiation horn were 10 mm and 20 mm, respectively. The mice were tied on the platform and continuously received irradiation until death. After immediate dissection, the mouse lung was quickly rinsed with 0.9% NaCl solution, fixed in 10% formaldehyde solution and mounted for paraffin section. After HE staining and image taken with a CCD camera, the Image Pro Plus software and quantitative image analysis by combining the mean optical density and area was used to determine the pathological injuries of the lung. Result Using the HA23. 16 and HA9. 92 pyramid horns with different physical parameter, the mice exposed to irradiation with high mean power of 12 W were dead most quickly, the death time was only about 110 s. Meanwhile, the death time was about 30 min after irradiation with the mean power of 5 W. There was significant hemorrhage in the mouse lung with high power millimeter irradiation, although the hemorrhage degree was different under different irradiation parameters. When the mean power were 10 and 12 W.the hemorrhage degree of lung was extremely high, where the bronchia and blood vessel of lung was markedly broken. A lot of cells of bronchia had been released. However, when the mean power was 5 W, the hemorrhage degree of lung was less observed, while the bronchia and blood vessels had not severe fracture. Conclusions High power millimeter wave wave irradiation has remarkable effect on mice lung. The damage degree of lung tissue is highly correlated with the mean power of millimeter wave irradiation. As the high power millimeter used in this study could result in significant thermal effect, the acute heat-induced response might lead to animal death by causing serious lung injury.