Abstract： Objective To study the expression of intercelluler cell adhesion molecule-1 (ICAM-1) , Interleukin-10(1L-10)and the activation of transcription factor activator protein-1 (AP-1 )in a rabbit model of ventilator-induced lung injury ( VILJ) and therefore to explore their possible role in VILI. Methods The VILI model was established by mechanical ventilation with a large tide volum (VT ) of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups: a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large VT for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 ( sICAM-1 ) and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay ( ELISA) . The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction ( RT-PCR). The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay ( EMSA). The partial arterial blood pressure of oxygen (PaO2) , myeloperoxidase (MPO) in lung homogenate, wet lung weight to dry lung weight ratio (W/D) were observed. Results (l)The concentrations of sICAM-1 in large VT for 2 h group (23 ±5) ng/L and 4 h group(35 ±5) ng/L were higher than that in the conventional ventilation group( 16 ±4)ng/L(P all < 0. 05) ,and that in the Large VT for 4 h group were higher than that in 1 h group(19 ±4)ng/L and 2 h group (P all < 0.01). The concentrations of IL-10 in the large VT for 2 h group (24 ±4) ng/L and 4 h group(26 ±5) ng/L were higher than that in the conventional ventilation group(15 ±2)ng/L(P all <0. 05) , and that in the Large VT for 4 h group was higher than that in the 1h group( 19 ±4)ng/L(P <0.05). The level of ICAM-1 mRNA in the large VT for 2 h group (1. 18 ± 0. 19) and 4 h group (1. 29 ±0. 19) were higher than that in the conventional ventilation group (0. 84±0. 13)(Pall<0. 05) ,and that in Large VT for 4 h group was higher than that in 1 h group(0. 96 ±0. 24) (P <0. 05). The level of IL-10 mRNA in the large VT for 4 h group (1. 13 ±0. 17) was higher than that in the conventional ventilation group(0. 84 ±0. 20) and Large VT for 1 h group(0. 86 ±0. 12) (P all < 0. 05). (2)The DNA-binding activity of AP-1 in the large VT for 2 h group (33. 77 ± 8. 23) and 4 h group (38 ±9) were higher than that in the conventional ventilation group (23 ±9)(Pall<0. 01) ,and that in Large VT for 4 h group was higher than that in lh group (25 ±9)(P<0. 01). (3) Histopathological findings demonstrated that diffused alveolar damage induced by mechanical ventilation was worse with time, and after mechanical ventilation with large VT for 2 h, the level of MPO began to increase, and for 4 h the PaO2 reduced and the W/D increased . Conclusions ICAM-1 and IL-10 took part in the inflammatory responses of VILI, and their up-regulation maybe due to the increase of their mRNA. Nuclear transcription factor AP-1 maybe involved in the transcriptional regulation mechanisms of these inflammatory mediators.