Objective The aim of this study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cells (huc-MSCs) and their lysates (huc-MSCs-lysate) on pulmonary fibrosis (IPF) in SD rats.Methods The SD rats were randomly divided into PBS group, 3 mg/kg BLM group, 5 mg/kg BLM group, and 10 mg/kg BLM group. They were sacrificed on the 10th and 21st days respectively to determine the optimal induction concentration and treatment time for establishing the IPF model in SD rats. After successfully establishing the rat IPF model, PBS, huc-MSCs, and huc-MSCs-lysate were used for atomization treatment on IPF rats respectively, and the pathological changes of lung tissue were evaluated. The expression of Smad3 was detected by IHC staining. Results BLM at 3, 5, and 10 mg/kg successfully established the rat model of pulmonary fibrosis, and fibrosis formed on the 10th day. Compared with the PBS group, the inflammation and collagen fiber deposition were alleviated in huc-MSCs group and huc-MSCs-lysate group. The pathological changes of huc-MSCs-lysate group were lighter and the content of Smad3 was significantly lower than that of PBS group.Conclusion 3 mg/kg BLM was used to establish a SD rat model of IPF. On the 10th day of treatment as the intervention time point, both huc-MSCs and huc-MSCs-lysate atomization treatment can reduce the degree of pulmonary fibrosis in BLM-induced IPF rat model, and huc-MSCs-lysate is more effective