Objective To study the effect of PM2.5 exposure on hepatic lymphangiogenesis in C57BL/6J mice and metabolic-associated fatty liver disease model mice, and to provide a novel target for prevention and treatment of PM2.5-induced liver injury. Methods Forty male C57BL/6J mice were randomly divided into: control group, PM2.5 group, metabolic-associated fatty liver disease (MAFLD) group and PM2.5-MAFLD group. Mice in the MAFLD group and PM2.5-MAFLD group were fed with high-fat diet for 12 weeks, mice in the other groups were fed with normal chow diet. From 13 weeks to 16 weeks, mice in the PM2.5 group and PM2.5-MAFLD group were treated with PM2.5 by tracheal instillation (twice per week); and mice in the mice in the other groups were instilled with saline at the same time. All animals were killed 24 h after the last PM2.5 treatment. Serum ALT and AST were measured, and the expression of LYVE1 of liver tissues were?visualized using immunofluorescence staining. The levels of hepatic oxidative stress markers (4-HNE and GSH/GSSG) were measured. The protein expression levels of lymphangiogenesis markers (PROX1 and LYVE1), lymphangiogenesis regulatory protein VEGF-C and lymphatic junctional function VE-cadherin in liver tissue were determined using Western blot. Results PM2.5 exposure significantly increased the levels of serum AST and ALT, and obviously decreased the protein expressions of PROX1，LYVE1 and increased the protein expression of VEGF-C, and VE-cadherin in liver, as well as increased the level of 4-HNE and decreased the ratio of T-GSH/GSSG in liver of mice in the MAFLD group (P<0.05). However, PM2.5 exposure did not affect the levels of serum AST and ALT, the protein expressions of PROX1，LYVE1, VEGF-C and the level of 4-HNE and the ratio of T-GSH/GSSG in liver of the MAFLD model mice (P<0.05). Conclusions PM2.5 exposure obviously aggravated hepatic oxidative injury, reduced hepatic lymphangiogenesis through reducing VEGF-C in the liver of MAFLD model mice.