Objective The effects of combined exposure to PM2.5 and high-salt diet on hepatic inflammation and lymphangiogenesis in mice. Methods Thirty-two C57BL/6J mice were randomly assigned to: control group, PM2.5 group, high-salt group and PM2.5+high-salt group. Mice in the high-salt group and PM2.5+high-salt group were fed with 8% high-salt diet for 8 weeks, mice in the other groups were fed with control diet containing 0.4% salt. Mice in the PM2.5 group and PM2.5+high-salt group were treated with PM2.5 by tracheal instillation (twice per week); and mice in the mice in the other groups were instilled with equal volume of saline at the same time (twice per week). All mice were sacrificed after the last PM2.5 exposure. TNF-α and IL-6 in liver tissues of mice were determined. Moreover, the LYVE1 expression of liver tissues were?visualized using immunofluorescence staining. The protein expression levels of lymphangiogenesis markers PROX1 and LYVE1, lymphangiogenesis regulatory proteins VEGFR-3 and VEGF-C in liver tissue were measured using Western blot. Results Compared to the control group, the levels of TNF-α and IL-6, as well as the protein expressions of PROX1，LYVE1, VEGFR-3 and VEGF-C in liver tissues of mice in the high-salt group (HSD) were obviously increased (P<0.05). Compared to the HSD, the levels of TNF-α and IL-6 and the protein expressions of PROX1，LYVE1, VEGFR-3 and VEGF-C in liver tissues of mice in the PM2.5+HSD were obviously increased (P<0.05). Moreover, there were significant interaction effects between PM2.5 and high-salt diet on these above indicators. Conclusions Combined exposure of PM2.5 and high-salt diet obviously aggravated hepatic inflammation, and may increase hepatic lymphangiogenesis through upregulating VEGFR-3 and VEGF-C in the liver of mice.