Objective To investigate the effect of tumor necrosis factor-α(TNF-α)on cytokines expression in mice with different tidal volume(VT). Methods Thirty six SPF male BALB/c mice were randomly divided into three groups:A group(spontaneously breathed 4 h),S and L group(mechanically ventilated 4 h,VT=6 mL/kg and VT=20 mL/kg). The three groups were then randomly divided into two subgroups(C and T group,n=6). Mice in C group were injected with NS,while that of T groups were injected with TNF-α at 20 μg/kg from tail intravenous. Morphological manifestation was observed by hematoxylin and eosin staining. Ultrastructure of macrophages were examined by transmission electron microscopy. The expression of TNF-α,interleukin(IL)-1β,IL-6,IL-10 in serum and BALF were measured by ELISA. The expression of NF-κB mRNA and protein were detected by RT-PCR and WB,respectively. Results Compared with A and S group,following could be observed under light microscope in L group:the pulmonary interstitial edema,consolidation of part of the lung tissue,alveolar space fusion and a number of inflammatory cells infiltration. The expression of TNF-α,IL-1β,IL-6,IL-10 in serum and BALF,the expression of NF-κB mRNA and protein in macrophages of L group were significantly higher than those of A and S group(both P<0.05). The expression of these cytokines and NF-κB mRNA and protein were increased in T group (P < 0.05). The expression NF-κB is positively correlated with the expression of TNF-α,IL-1β and IL-6. Conclusion TNF-α is a key factor in inflammation of ventilation induced lung injury,which may provide a new method for prevention of VILI in clinical practice.