Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide and clinically is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The exact cause of PD remains unknown; however, early neurodegeneration in PD has been associated with microglia activation and loss of blood-brain barrier (BBB) integrity. The serine protease tissue plasminogen activator (tPA) is known to be a key regulator of BBB integrity. Recently, our laboratory discovered that the integrin Mac-1 expressed on microglia is necessary for tPA-mediated BBB dysfunction in the brain. These findings suggest a possible unifying role of tPA in BBB regulation and early innate immune response in the brain under pathological conditions such as PD. Therefore, my research interest is to explore the role of BBB and microglia regulation mediated by tPA in PD progression.