ObjectiveTo investigate the effect and mechanism of ulinastatin to ventilator induced lung injury (VILI). MethodsTotal 24 SD rats were randomly divided into a control group, a VILI group, and a VILI+ ulinastatin group. High mobility group box-1 (HMGB-1), tumor necrosis factor (TNF)-α and interleukin (IL)-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were detected in the three groups. ResultsHMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were significantly higher in the VILI group than those in the control group with statistical differences (P<0.05). While HMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were reduced in the VILI+ ulinastatin group compared with those in the VILI group. ConclusionUlinastatin may protect ventilator induced lung injury by reducing inflammation level in lung through HMGB-1-TLR4 pathway.