The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which crosses the blood-brain barrier (BBB) and destroys dopaminergic neurons, is commonly administered to animals to model Parkinson’s disease (PD). While the destructive effects of MPTP on dopaminergic cells are well established, recent evidence suggests that MPTP may also compromise the integrity of the cerebral vasculature, although the timeline of vascular damage remains unclear. Our team has demonstrated that photobiomodulation (PBM) – the irradiation of tissue with low-intensity red to near-infrared light – mitigates MPTP-induced damage to the nigrostriatal pathway, but the effects of PBM on the brain vasculature have not been investigated. In this study, we aimed to delineate the time course of cerebrovascular disruption as a result of MPTP intoxication, and to determine whether PBM could mitigate this disruption. Male C57BL/6 mice were injected with 80 mg/kg MPTP, in 4 injections over 6 hours (n=20), or a corresponding volume of saline vehicle (n=8). At 1, 2, 3, 7 or 14 days after injection, mice were euthanased and perfused transcardially with FITC-albumin tracer (5 mg/ml). Fluorescence microscopy of coronal sections of the substantia nigra pars compacta (SNc) and caudate-putamen complex (CPu), followed by analysis of the proportion of pixels positive for FITC, revealed maximum vascular leakage at 7 days post-injection for both the SNc (3.2±0.2 vs 15.7±0.4, p<0.0001) and CPu (2.9±0.2 vs 26.2±1.4, p<0.0001). In a separate cohort of mice injected with 80 mg/kg MPTP (n=12) or saline (n=8), a subset of MPTP mice (n=6) received daily transcranial PBM, commencing 24 hours after the final MPTP injection. PBM was directed at the cranium using a handheld LED panel (WARP10; 670 nm, 50 mW/cm2, 180 s daily), and tissue was collected 7 days post-injection. Transcranial PBM significantly mitigated MPTP-induced vascular leakage in both the SNc (19.9±1.7 for MPTP-sham vs 7.9±1.4 for MPTP-PBM, p<0.0001) and the CPu (30.2±1.7 vs 13.4±3.9, p=0.0005). Vascular leakage in PBM-treated MPTP mice was not significantly greater than saline-injected control mice (SNc: 5.6±0.6, p=0.38; CPu: 5.9±0.4, p=0.07). This study has demonstrated that (i) the neurotoxin MPTP, which is used to model PD, induces transient cerebrovascular permeability that peaks at ~7 days post-injection, and (ii) that post-conditioning with daily transcranial PBM can mitigate cerebrovascular damage in this model. The observed disruption of blood-brain barrier integrity following MPTP exposure brings into question the validity of using the MPTP model for pre-clinical trials of pharmacological PD treatments. While further research is required to understand the mechanism of action, the discovery that PBM can mitigate MPTP-induced BBB disruption provides the rationale for more widespread deployment of this neuroprotective intervention for conditions that involve vascular damage, such as stroke and traumatic brain injury.