AIM: To explore the role of imbalance of local renin-angiotensin system (RAS) in lung injury by observing the changes of angiotensin Ⅱ type 1 receptor (AT1R) and Mas receptor protein expression in the lung and the degree of lung injury subject to limb ischemia-reperfusion (LIR) in the mice.METHODS: Male ICR mice (n=42, 8 weeks old) were randomly assigned into 7 groups (6 in each group), including control group and 6 model groups with LIR of 0.5 h, 1 h, 2 h, 4 h, 6 h and 12 h reperfusion.Tourniquets were used to block the blood flow of the hind limbs of the ICR mice and were released after 2 h ischemia to initiate reperfusion.The mice were sacrificed by eyeball blood withdrawal at different time points after reperfusion.The organ coefficient and wet/dry weight ratio (W/D) of the lung tissue were calculated.Bronchoalveolar lavage fluid (BALF) was taken for cell counting and protein concentration measurement.The histopathological changes of the lung tissues was observed, and the pathological score was calculated.The protein expression of AT1R and Mas receptor in the lung tissues was determined by Western blot.RESULTS: The organ coefficient, W/D of lung tissue, and cell number and protein concentration in BALF of model groups were significantly higher than those in control group after LIR.The pathological changes were found in the lung tissue of model mice, including alveolar capillary dilation and congestion, edema, inflammatory cell infiltration in peripheral vascular, alveolar and bronchial walls, alveolar septal thickening and inflammatory cell infiltration.The lung injury score was elevated gradually along with the extension of reperfusion time.The protein expression of AT1R began to increase at reperfusion time points of 0.5 h and 1 h.With the extension of reperfusion time, the protein expression of AT1R decreased gradually.Conversely, the protein expression of Mas receptor increased gradually with prolonged reperfusion.CONCLUSION: LIR induces acute lung injury gradually.The imbalance of AT1R and Mas receptor expression may be involved in the damage process.