Objective To evaluate the effect of propofol (PPF) on stress response and lung injury in rats with traumatic brain injury (TBI).Methods A total of 36 SD rats were randomly (random number)divided into sham group,intralipid group,TBI group,PPF1 h group,PPF 2 h group,PPF 6 h group (n =6 in each group).Fluid percussion brain injury models were used.By intraperitoneal injection,intralipid was administered in intralipid group after sham operations,while propofol 100 mg · kg-1 was given to rats in PPF1 h group,PPF 2 h group and PPF 6 h group 1,2,6 hours following injury,respectively.Nerve motor function were scored at different intervals,serum concentrations of adrenocorticotropic hormone (ACTH),cortisol (COR) and norepinephrine (NE) were measured 12 h after injury.Seventy-two hours later,all rats were sacrificed and brains were harvested for TTC staining,and lungs taken were stained with HE staining for observation under light microscope and electron microscopy.Results Compared with sham and intralipid group,nerve motor function scores were significantly decreased,and serum concentrations of ACTH,COR and NE were increased significantly in rats after injury.Compared with TBI group,the above biomarkers were improved significantly after propofol injection.There were no significant differences in above biomarkersbetweenPPF 1 hand PPF 2 h group (t=-0.816,t=-0.208,t=0.582,P＞0.05).The differences in COR and NE concentrations between PPF 2 h and PPF 6 h group were statistically significant (t =3.018,P =0.013;t =3.662,P =0.004).Light microscopy demonstrated abundant inflammatory cell infiltration and massive thickening of the alveolar walls,Electron microscopy showed Type Ⅱ lung epithelial cell swelling,vacuolar degeneration,osmiophilic lamellar corpuscle emptying in cytoplasm,microvilli protrusions decreases in some cytoplasm in TBI group,and pathological damage was improved significantly in PPF 2 h group.Conclusions Propofol may inhibit stress and protect the lung tissue from damage in TBI rats.