Objective To investigate the effect of mechanical ventilation on the pulmonary microvascular permeability in diabetic mice.Methods Sixty-four male C57/BL6 mice aged 10-12 months,weighing 20-25 g,were randomly assigned into 4 groups (n =16 each):control group (group C); mechanical ventilation group (group M); diabetes group (group D); diabetes mechanical ventilation group (group DM).Diabetes was induced by intraperitoneal streptozotocin 150 mg/kg (in citric acid buffer solution 0.1 mol/L) and confirmed by blood glucose level ＞ 16 mmol/L in groups D and DM,while the equal volume of citric acid buffer solution was given instead of streptozotocin in groups C and M.The animals were anesthetized with intraperitoneal pentobarbital 100 mg/kg and tracheostomized.The animals kept spontaneous breathing for 4 h in groups C and D,while the animals were mechanically ventilated for 4 h in groups M and DM.Eight mice from each group were randomly selected,arterial blood samples were obtained for blood gas analysis,and then the animals were sacrificed and the lung tissues were removed for determination of microscopic examination,W/D lung weight ratio and myeloperoxidase (MPO)activity.Four mice from each group were sacrificed and the pulmonary vascular permeability was determined.Four mice from each group were sacrificed and the primary pulmonary microvascular endothelial cells (PMVECs) were cultured in vitro and confirmed.The PMVEC permeability coefficient was measured using transendothelial [ 14 C ]BSA flux.Results Compared with group C,PaO2 was significantly decreased,and the MPO activity,pulmonary microvascular permeability and PMVECs permeability coefficient were significantly increased in groups M,D and DM,and W/D lung weight ratio was significantly increased in groups M and DM ( P ＜ 0.05).PaO2 was significantly lower,and W/D lung weight ratio,MPO activity,pulmonary microvascular permeability and PMVECs permeability coefficient were significantly higher in group DM than in group D ( P ＜ 0.05).Conclusion The mechanism by which mechanical ventilation induces lung injury may be related to the increase in the pulmonary microvascular permeability in diabetic mice.