Objective To estimate the effect of endothelial progenitor cells (EPC) on acute rejection induced by lung transplantation. Methods Twenty-four rats were randomized into sham (S), control (C) or EPC group (n=8). The rats in S group only received intubation and mechanical ventilation. The rats in C and EPC groups received left lung transplantation. The PaO2/FiO2, lung wet/dry weight ratio, protein contents in lung tissue were detected. The ICAM-1 and LFA in serum, and IFN-γ, IL-2 and IL-10 in transplanted lung tissue were measured. The score of rejection and histological were estimated. Results Compared with C group, the PaO2/FiO2 was increased, and the wet/dry weight ratio and protein concentration were decreased in EPC group (P<0.05). The ICAM-1 and LFA in serum, and IFN-γ and IL-2 in transplanted lung tissue were down-regulated, but the IL-10 was up-regulated by the EPC (P<0.05). compared with C group, the rejection score and histological injury were improved by the EPC after lung transplantation (P<0.05). Conclusion The EPC significantly reduced the lung acute rejection after lung transplantation. The protection of EPC on rejection mainly due to the regulation of EPC on inflammation.