Pulmonary fibrosis represents the end-stage pathological change of various interstitial lung diseases, often resulting from alveolar injury and dysregulated repair process. Our previous study found that human embryonic stem cells-derived immunity-and-matrix-regulatory cells (IMRCs), expressing high level of leukemia inhibitory factor (LIF), effectively mitigated bleomycin-induced pulmonary fibrosis in a mouse model. To elucidated the regulatory role of LIF in pulmonary fibrosis, we applied recombinant LIF in vitro and in vivo models. Our data demonstrated that recombinant LIF can inhibit MRC-5 fibroblast activation and α-SMA expression during epithelial-mesenchymal transition in A549 cells. Administration of LIF in a bleomycin-induced pulmonary fibrosis mouse model, either during the alveolar injury phase (days 0-2) or the fibrosis phase (days 9-11) post-bleomycin administration alleviated pulmonary fibrosis by day 21. Moreover, our study observed a modulation of inflammatory factors with a concurrent downregulation of Tnf, Cxcl10, and Ccl22.