Methamphetamine (meth) is a potent psychostimulant known to cause neurotoxicity. Clinical reports suggest meth abuse is a risk factor for Parkinson’s disease. We investigated changes in the blood–brain barrier and cerebral vasculature as a mechanism underlying this risk in rats treated acutely and trained to self-administer meth. We observed blood–brain barrier leakage in rats treated acutely with meth. Hypoperfusion in the striatum was detected with acute and chronic meth treatment and was associated with hypoxia. This was correlated with reductions in striatal tyrosine hydroxylase in rats trained to self-administer meth. These findings suggest a new mechanism of meth-induced neurotoxicity involving striatal vasoconstriction resulting in hypoxia and dopamine reductions leading to an increased risk for Parkinson’s disease for meth abusers.