This study aimed to evaluate the effects of acrylonitrile (ACN) on neuronal morphology and apoptosis in rats. An ACN solution was administered to Wistar rats by gavage at doses of 0, 5, 10, or 20 mg/kg, 5 days a week for 13 weeks. The morphology of neurons and the presence of apoptosis was examined by light and electron microscope, DNA electrophoresis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Significant vacuolation and the widening of the interspaces around blood vessels were observed in the groups that received the highest dose. Disordered myelin sheaths, malformed neuronal nuclei, and chromatin condensation at the periphery of the nucleus that formed crescents were also observed in the treated rats. The number of apoptotic neurons was significantly decreased (P < 0.05) in the treated groups (5 mg/kg group: 1.5 ± 1.22 apoptotic neurons/slide; 10 mg/kg group: 2.5 ± 1.05 apoptotic neurons/slide; 20 mg/kg group: 2.34 ± 1.21 apoptotic neurons/slide) compared to the control group (4.5 ± 1.52 apoptotic neurons/slide). The number of Bcl-2-positive neurons and the levels of staining were increased in the treated rats compared to those of the control group. These results suggested that ACN may induce serious morphological changes in rat neurons and inhibit neuronal apoptosis in rats.