The salient features of our study are: (1) n-hexane exposure resulted in loss of dopaminergic neurons in rats; (2) microglial activation preceded dopaminergic neurodegeneration and depletion of microglia reduced HD-induced dopaminergic neurotoxicity; (3) HD exposure stimulated activation of NOX2 by inducing membrane translocation of cytosolic subunit p47phox; (4) integrin αMβ2 contributed to HD-induced NOX2 activation through a Src-Erk-dependent pathway; and (5) pharmacological inhibition of αMβ2-NOX2 axis protected dopaminergic neurons against HD-induced toxicity. Here, SRC is linked to Huntington disease.