Objective To investigate the effects of combined exposure to PM2.5 and a high-salt diet on hepatic inflammation and lymphangiogenesis in mice. Methods Thirty-two C57BL/6J mice were assigned randomly to control, PM2.5, high-salt(HSD), and PM2.5+HSD groups. Mice in the HSD and PM2.5+HSD groups were fed an 8% high-salt diet for 8 weeks, while mice in the other groups were fed a control diet containing 0.4% salt. Mice in the PM2.5 and PM2.5+HSD groups were treated with PM2.5 by tracheal instillation (twice per week), and mice in the other groups were instilled with equal volumes of saline (twice per week). All mice were sacrificed after the last PM2.5 exposure. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in the liver tissues of the mice were determined and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) expression in the liver tissues was visualized by immunofluorescence staining. Protein expression levels of the lymphangiogenesis markers PROX1 and LYVE1, and the lymphangiogenesis regulatory proteins vascular endothelial growth factor (VEGF) receptor (VEGFR) 3 and VEGF-C in liver tissue were measured by Western blot. Results TNF-α and IL-6 levels and protein expression levels of PROX1, LYVE1, VEGFR-3, and VEGF-C in liver tissues were increased in the HSD group compared with the control group (P<0.05), and in the PM2.5+HSD group compared with the HSD group (P<0.05). Moreover, there were significant interaction effects between PM2.5 and a high-salt diet on these above indicators. Conclusions Combined exposure to PM2.5 and a high-salt diet aggravated hepatic inflammation and may increase hepatic lymphangiogenesis by upregulating VEGFR-3 and VEGF-C in liver of mice.