Objective To characterize the transcriptomic features of pulmonary fibrosis in young and aged mice, identify the core regulatory pathways in aged lung fibrosis using weighted gene co-expression network analysis (WGCNA), and further investigate the therapeutic mechanisms of Wenfei Huaxian Decoction (WHD) in aged mice with pulmonary fibrosis. Methods Pulmonary fibrosis models were induced by intratracheal instillation of bleomycin (BLM) in 2-month-old (young) and 18-month-old (aged) mice. Transcriptome sequencing combined with kyoto encyclopedia of genes and genomes (KEGG) enrichment, gene set enrichment analysis (GSEA), and WGCNA was performed to identify age-related pathways. For the in vivo verification of WHD efficacy, aged model mice were treated with WHD, followed by HE and Masson staining to assess lung histopathological. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of senescence-associated secretory phenotype (SASP) factors, and Western blot conducted to evaluate the protein expression of senescence markers (p53, p21), myofibroblast marker α-smooth muscle actin (α-SMA). Results Transcriptomic analysis revealed that BLM-induced young model mice showed features of acute injury repair, immune cell activation, and mild matrix remodeling. In contrast, aged model mice exhibited excessive extracellular matrix deposition, myofibroblast activation, and chronic inflammatory accumulation-processes strongly associated with the p53 signaling pathway. WGCNA identified a gene co-expression module highly correlated with age (r = 0.96, P < 0.001), and KEGG enrichment of this module further highlighted significant enrichment of the p53 pathway. Experimental validation showed that WHD significantly alleviated BLM?induced alveolitis and fibrosis, reduced SASP factor levels (P < 0.05), and downregulated the expression of p21, p53, and α?SMA (P < 0.05). Conclusion WHD exerts a protective effect against BLM-induced pulmonary fibrosis in aged mice, and its underlying mechanism may be associated with the modulation of the p53 signaling pathway, thereby reducing cellular senescence and excessive SASP secretion, and ultimately suppressing myofibroblast activation.