Objective　To evaluate the effect of Shenfu injection(SF) on ventilator-induced lung injury in rats and its mechanism.　Methods　Forty adult male Wister rats were equally and randomly divided into 4 groups(n=10) using a random number table :control group(group C), normal tidal volume ventilation group(group N), large tidal volume ventilation group(group L), and large tidal volume ventilation+SF group(group SF). The spontaneous breathing of rats was maintained in group C, while the other rats were tracheostomized and mechanically ventilated for 4 h in group N, group L and group SF. Rats were killed at the end of the ventilation and was lavaged their left lung, then the bronchoalveolar lavage fluid(BALF) was collected for determination of the concentrations of protein, IL-1β, IL-18 and TNF-α. The lung tissues were removed for determination of the wet/dry(W/D) lung weight, and immunohistochemistry was used to detected the expression of NF-κB. The pathological changes of the lungs were determinated by using light microscope and the lung injury scores were also determinated.　Results　Compared with group SF［TNF-α (65±11) ng/L, IL-1β (47±9) ng/L, IL-18 (58±8) ng/L］, the protein expression level of IL-1β, IL-18 and TNF-α in BALF were significantly increased in group L［TNF-α (99±7) ng/L, IL-1β (69±7) ng/L, IL-18 (86±7) ng/L］(P<0.05). W/D (5.0±1.6) in group SF were significantly decreased while W/D (5.5±1.8) in group L (P<0.05). The protein expression level of NF-κB were (0.32±0.28) in group SF while (0.54±0.33) in group L. The protein expression level of NF-κB were significantly decreased in group SF (P<0.05) and the pathological changes were also significantly reduced in group SF.　Conclusions　SF can reduce ventilator-induced lung injury in rats and its mechanism may be related to the inhibition of the activity of NF-κB pathway and reducing the release of inflammatory cytokines in the lungs.