Objective To study the effect of fine particulate matter (particulate matter 2. 5, PM2. 5) exposure on hepatic lymphangiogenesis in C57BL/ 6J mice and metabolic-associated fatty liver disease (MAFLD) 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 a control group, PM2. 5 group, MAFLD group, and PM2. 5-MAFLD group. Mice in the MAFLD and PM2. 5-MAFLD groups were fed high-fat diet for 12 weeks, and mice in the other groups were fed normal chow diet. From weeks 13 to 16, mice in the PM2. 5 and PM2. 5-MAFLD groups were exposed to PM2. 5 by tracheal instillation (twice per week), and mice in the other groups were instilled with saline at the same time. All animals were euthanized 24 h after the last PM2. 5 instillation. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the expression of LYVE1 in liver tissues was visualized using immunofluorescence staining. Hepatic oxidative stress markers levels ( 4-HNE and GSH/ GSSG ) were measured. The protein expression levels of lymphangiogenesis markers ( PROX1 and LYVE1), lymphangiogenesis regulatory protein VEGF-C, and the lymphatic junctional function marker VE-cadherin in liver tissue were determined using Western Blot. Results PM2. 5 exposure significantly increased the levels of serum AST and ALT, markedly decreased the protein expression of PROX1 and LYVE1, increased the protein expression of VEGF-C and VE-cadherin in the liver, increased the level of 4-HNE, and decreased the T-GSH/ GSSG ratio in livers of mice in the MAFLD group (P<0. 05). However, PM2. 5 exposure did not affect the levels of serum AST and ALT, protein expression of PROX1, LYVE1, or VEGF-C; level of 4-HNE; or T-GSH/ GSSG ratio in the livers of the C57BL/ 6J mice (P>0. 05). Conclusions PM2. 5 exposure obviously aggravated hepatic oxidative injury and reduced hepatic lymphangiogenesis by reducing the VEGF-C concentration in the livers of MAFLD model mice.