Objective The aim of this study is to explore the mechanism of alveolar wall remodeling mediated by vascular endothelial growth factor (VEGF) through the p38 MAPK signaling pathway, in order to reveal its potential role in lung diseases. Methods VEGF at different concentrations (2.5, 5, 10, 20, 40 ng/mL) was applied to HPAEpiC cells, and a pulmonary fibrosis cell model was constructed using bleomycin. The effects of VEGF on the proliferation, apoptosis, and extracellular matrix proteins of HPAEpiC cells were detected by CCK-8 assay and immunofluorescence staining assay. WB and qRT-PCR were used to analyze the activation of the p38 MAPK pathway by VEGF. Results Low concentration VEGF can promote the proliferation of HPAEpiC cells; High concentrations of VEGF inhibit the proliferation of HPAEpiC cells, promote cell apoptosis, and increase the content of extracellular matrix proteins; At the same time, it was found that VEGF treatment of HPAEpiC cells upregulated the expression of p38 MAPK, p-p38 MAPK, ERK, JNK proteins and mRNA in the cells (P<0.05). In addition, using VEGF to treat a mouse model of pulmonary fibrosis can exacerbate the condition of pulmonary fibrosis in mice. Conclusion VEGF may regulate the synthesis of extracellular matrix proteins in alveolar walls and promote alveolar wall remodeling by activating the expression of the p38 MAPK signaling pathway.