Objective: To investigate the protective effect and mechanism of ischemic preconditioning (IP) on the rat lung ischemia-reperfusion injury (IRI). Methods: Forty-five specific pathogen-free SD rats were randomly divided into Sham group (n = 15), ischemia-reperfusion group (I/R group, n = 15) and IP + IR group (n = 15). All groups were dealt differently. The pathological changes and apoptosis of the lung tissue were observed, and its water content was measured. Additionally, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and endothelin-1 (ET-1) concentrations in serum and lung tissue homogenate were detected. Results: Compared with Sham group, the lung tissue lesions obviously became worse, apoptotic number, water content in the lung tissue, MDA and ET-1 concentrations in serum and lung tissue all increased significantly, while SOD activity decreased markedly in I/R group under a light microscope (P < 0.01). By comparison to I/R group, the lung tissue lesions got better, apoptotic number, water content in the lung tissue, MDA and ET-1 concentrations in serum and lung tissue all decreased significantly, while SOD activity decreased markedly in IP + I/R group (P < 0.01). Conclusion: IP has a protective effect on IRI, and this effect may be related to activation of endogenous antioxidation, inactivation or reduction of oxygen free radicals and protection of pulmonary vascular endothelial injury.