The blood-brain barrier (BBB) is a layer between the blood circulation and neural tissue. It plays a pivotal role in maintaining the vulnerable extracellular microenvironment in the neuronal parenchyma. Neuroinflammatory events can result in BBB dysregulation by disturbing adherens junctions (AJs) and tight junctions (TJs). VE-cadherin, as one of the most important components of the vascular system, is specifically responsible for the assembly of AJs and BBB architecture. Here, we present a review, which highlights recently available insights into the relationship between the neuroinflammation and BBB dysregulation. We then explore the specific interaction between VE-cadherin and BBB. Finally, we discuss the changes of VE-cadherin with different neurological diseases from both experimental and clinical studies. An understanding of VE-cadherin in BBB regulation may indicate that VE-cadherin can partially be a biomarker of neuroinflammation disease and lead to novel approaches for abating BBB dysregulation under pathological conditions and the opening of the BBB following central nervous system (CNS) drug delivery.