Abstract： Background Irradiation dose and volume are the major physical factors of radiation-induced lung injury.The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.Methods Animals were randomly assigned to three groups.The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume.The treatment plan for the three groups was:group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm3 (25% lung volume);the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy,respectively (bilateral AP-PA fields,source to axis distance (SAD)=100 cm,6MVX,single irradiation);Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm3 (100% lung volume);the total dose was 1153 cGy.MLD was 2006 cGy,which was the same as that of group 1 (bilateral AP-PA fields,SAD = 100 cm,6MVX,single irradiation);Group 3 was a control group.With the exception of receiving no irradiation,group 3 had rest steps that were the same as those of the experimental groups.After irradiation,functional,histopathological,and CT changes were compared every two weeks till the 16th week.Results Functionally,after irradiation breath rate (BR) increases were observed in both group 1 and group 2,especially during the period of 6th-8th weeks.The changes of BR in the 100% volume group were earlier and faster.For the 25% volume group,although pathology was more severe,hardly any obvious increase in BR was observed.Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week).The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group,and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion,pleural thickening,and lung shrinking.Morphologically,the 100% volume group mainly presented signs of vascular damage,including signs of vascular wall edemas,hypertrophy,and sclerosis.The 25% volume group mainly presented with erythrocyte cell exudation,inflammation,and parenchymal damage.Conclusions The delivery of a small dose of radiation to a large volume is not safe.A low dose smeared out over large volumes,albeit reversible,may lead to fatal respiratory dysfunction.Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose.Clinically,the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.