In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. This evidence concerns the gene TGFB1 and pulmonary fibrosis.