Abstract: Objective To explore the protection effect and mechanism of stem cell mobilization on pulmonary surfactant of chronic obstructive pulmonary disease (COPD) rats. Methods Forty Wistar rats were randomly divided into GOPD group (n=20) and COPD-rhG-CSF group (n=20). All the rats were prepared for COPD models by smoke and trachea injection of lipopolysaccharide (LPS); At the same time, the COPD-rhG-CSF group were injected recombinant human granulocyte-colony stimulating factor (rhG-CSF) through tail vein, and the GOPD group were injected same volume of saline. On 1st day, 14th day and 28th day after successful preparation, pulmonary tissue slices were prepared to observe the histopathological changes. Furthermore, CC16 and pulmonary surfactant protein A (SP-A) expression were observed by immunohistochemical experiment, RT-PCT assay and WB assay. Results After successful preparation, the pulmonary tissue slices showed that the alveolar reduced, the alveolar cavity extended irregularly and the alveolar interval fractured; and the COPD group was aggravating over time, but the COPD-rhG-CSF group was relieving compared to the COPD group. The immunohistochemical experiment showed that the CC16 and SP-A expression of the COPD-rhG-CSF group were higher than those of the COPD group in 1st day, 14th day and 28th day after the successful preparation, and the difference between groups had statistical significance (all P<0.05). The RT-PCR and WB assay results showed that the CC16 and SP-A expression of the COPD-rhG-CSF group were higher than those of the COPD group in 1st day, 14th day and 28th day after successful preparation, and the difference between groups had statistical significance (all P<0.05). Conclusion Stem cell mobilization can improve the CC16 and SP-A expression of COPD rats, and promote lung tissue repair, which maybe one of the important mechanisms to protect lung tissues.