BackgroundAfter stimulation due to injury, cell division cycle protein 42 (Cdc42) restores and enhances barrier functions by strengthening intercellular adherens junctions; however, its influence on cell proliferation after injury remains unknown. ObjectiveIn this study, we sought to investigate the effect of stimulation using small doses of lipopolysaccharide (LPS) on the proliferation of pulmonary microvascular endothelial cells (PMVECs). MethodsWe stimulated PMVECs with different doses of LPS and evaluated the effects on cell proliferation. We also constructed a primary gene-knockout cell line lacking Cdc42 to verify the role of Cdc42 in regulating the proliferation of PMVECs that were stimulated using LPS and to explore related signaling pathways. ResultsStimulating PMVECs with small doses of LPS increased proliferation. Cdc42 is involved in regulating this process, which was mediated by the extracellular regulated protein kinase (ERK) pathway. ConclusionsCdc42 plays a role in regulating the proliferation of PMVECs stimulated with small doses of LPS, and this regulation involves the ERK pathway.