Objective：To explore the effects of meningeal lymphatic vessel transport dysfunction on lipopolysaccharide（LPS）-induced central nervous system inflammation in mice. Methods：Firstly，sixteen C57BL/6 mice were randomly divided into four groups， normal saline was injected intraperitoneally in the Control group. The LPS groups were injected intraperitoneally with LPS（2 mg/kg）， and then the transport function of meningeal lymphatic vessels，activation of microglia and levels of interleukin-6（IL-6）and interleukin-1β （IL -1β）in the hippocampus were observed after 12 h，24 h and 72 h. Secondly，eight mice were randomly assigned to two groups： Control group and VEGFR3 inhibitor MAZ51 group，to observe the effects of MAZ51 on the transport function of meningeal lymphatic vessels. Finally，twenty-four mice were divided into four groups as follows：control group，MAZ51 group，LPS group，and LPS+MAZ51 group. MAZ51（10 mg/kg）was preinjected intraperitoneally into MAZ51 group and LPS+MAZ51 group for five days per week with a total of 30 days. After six weeks，LPS was injected into LPS group and LPS+MAZ51 group. A day later，behavioral experiments that assess the ability of mice to escape from fear were conducted；the activation of microglia in the hippocampus was measured by immunohistochemistry；the expression of IL-6 and IL-1β was evaluated by ELISA method. Results：The area of LYVE-1 in meninges and the area of OVA-647 in the deep cervical lymph nodes were significantly decreased 24 h after intraperitoneal injection of LPS（P < 0.01），and were lower than the basal level for 72 h（P < 0.01）. The activation of microglia and levels of IL-6 and IL-1β in the hippocampus were significantly increased after 24 h（P < 0.01）. Compared with the control group，the area of OVA-647 fluorescence in the MAZ51 group was significantly reduced（P < 0.01）. The activation of microglia and the expression of inflammatory factors in the hippocampus of mice in the LPS+MAZ51 group were increased（P < 0.01）and the freezing time was significantly reduced（P < 0.01）. Conclusion：The impairing transport function of meningeal lymphatic vessels aggravates LPS-induced central inflammation and cognitive dysfunction in mice by increasing inflammatory mediator accumulation and activating microglia.