Abstract： Objective To explore a minimally invasive,reliable,and efficient method for endotracheal intubation to instill lipopolysaccharide (LPS) for preparation of acute lung injury (ALI) in mice.Methods A total of 80 BALB/C mice was randomly selected into LPS group ( n =40) and control group (Normal saline,NS; n =40).After a successfully endotracheal intubation,each mouse was instilled by LPS (3 mg/kg) in LPS group,and NS ( 1.5 ml/kg) in NS group,respectively.The one-time success rate and final success rate of the endotracheal intubation,and survival rate were recorded.After 24 hours,the total number of cells in bronchoalveolar lavage fluid (BALF) of left lung was counted with light microscope.The cells were classified and counted after Wright's stain.Total protein concentration in BALF was assayed with a BCA kit.Wet/dry value was calculated after the lung became dry.Artery blood PaO2 was tested and the oxygenation index was counted.Results Compared to NS group,the LPS group had the one-time success rate 92.5％,and the final success rate 100％,survival rate 100％,the total number of cells [ ( 10.82±3.51) ×105/mlvs (0.72±0.52) ×105/ml.t =-6.294 P ＜0 01] the rate of polymorphonulear leukocytes in total cells [ (93.93 ± 1.77) ％ vs (2.2 ± 0.91 ) ％,t =- 105.565,P ＜ 0.01 ],the rate of mononuclear leukocytes in total cells[ (6.07 ± 1.77)％ vs (97.8 ±0.91 )％,t =- 105.565,P ＜0.01 ],total protein concentration[ (0.49 ± 0.13 ) mg/ml vs (0.29 ± 0.11 ) mg/ml,t =- 2.823,P ＜ 0.05 ],W/D ratio(4.60 ±0.18 vs 4.16 ±0.25,t =-4.793,P ＜0.01 ),PaO2[ (68.57 -±7.23)％ vs(87.00 ±6.33 )％,t =4.571,P ＜ 0.01 ],and oxygenation index [ (326.53 ± 34.43 )mmHg vs (414.29 ± 30.16)mmHg,t =4.571,P ＜0.01 ].Conclusions Improved method for endotracheal intubation has high success rate and minimal injury,and instillation of LPS (3 mg/kg)can induce mice ALI successfully.