Objective To investigate the mechanism of ginsenoside Rg3 ( GS-Rg3 ) regulation of lymphangiogenesis in nude mice bearing human lung cancer by the transforming growth factor-β1 (TGF-β1) / extracellular regulatory protein kinase (ERK) signaling pathway. Methods Sixty nude mice were randomly divided into three groups: model group, GS-Rg3 group and SCH772984 group. The orthotopic transplantation model of human lung cancer in nude mice was established in the GS-Rg3 and SCH772984 groups. The GS-Rg3 mice were gavaged with GS-Rg3. Mice in the SCH772984 group were intraperitoneally injected with the ERK inhibitor SCH772984. Modeling and lymphatic metastasis of each group of mice were observed. Lymphangiogenesis, TGF-β1/ ERK signaling pathway and vascular endothelial growth factor (VEGF) expression in tumor tissues of each group were analyzed. Results Pathological examination using HE staining confirmed the lung cancer and its lymphatic metastasis. The proportion of lymphatic metastasis, tumor volume and tumor mass in the GS-Rg3 group and the SCH772984 group were significantly lower than those in the model group. There was no significant difference between the GS-Rg3 group and the SCH772984 group. Podoplanin protein expression level and relative density of lymphatic vessels were significantly lower in the GS-Rg3 group and the SCH772984 group than in the model group when using the podoplanin protein to label lymphatic vessels. There was no significant difference between the GS-Rg3 group and the SCH772984 group. GS-Rg3 and SCH772984 significantly inhibited activation of the TGF-β1/ ERK pathway. The expression levels of VEGF-C and VEGF-3 in the GS-Rg3 group and the SCH772984 group were lower than those in the model group. There was no significant difference between the GS-Rg3 group and the SCH772984 group. Conclusions GS-Rg3 can inhibit the expressions of VEGF-C and VEGF-3 by downregulating the transduction level of the TGF-β1/ ERK signaling pathway, thereby inhibiting lymphangiogenesis and reducing the lymphatic metastasis rate of lung cancer.