To investigate the changes in the porcine vascular endothelial barrier during the exudative inflammation caused by Haemophilus parasuis (HPS), HPS was used to infect porcine vascular endothelial cells isolated from pigs. Western blot and indirect immunofluorescence analysis revealed that Wnt/β-catenin pathway mediated the disruption of the adherens junctions composed of β-catenin and VE-cadherin in HPS-infected porcine endothelial cells, resulting in a damaged endothelial cell barrier and increased monolayer endothelial cell permeability. Moreover, inhibition of VEGF expression significantly suppressed the nuclear translocation of β-catenin and markedly restored the intercellular adherens junctions composed of β-catenin and VE-cadherin, which benefits the recovery of endothelial cell permeability. These results suggested that HPS infection disrupted intercellular adherens junctions and increased endothelial cell permeability by activating the Wnt/β-catenin pathway in porcine endothelial cells; meanwhile, the VEGF gene downstream of the Wnt/β-catenin pathway amplifies the Wnt/β-catenin pathway activity and cell damage induced by HPS infection through a positive feedback.