Objective To investigate the neuron protective effects of ligustilide (LIG) on cortex regions of cerebral hypoperfusion rats and the possible mechanisms of the protective effect. Methods Bilateral common carotid arteries (two-vessel occlusion, 2VO) of Sprague-Dawley rats were occluded to induce the chronic cerebral hypoperfusion models. The sham-operated controls (Sham group) were not occluded. The model rats were treated with LIG (80 mg/kg, by oral) once a day from the 8^th day after surgery for 21 d. The rats were sacrificed 7 d after stopping LIG treatment, and the brain tissues of rats were made into frozen sections. Nissl staining, immunohistochemistry and immunofluorescence experiments were performed. Coronal sections of the cortex were stained with cresyl violet or with antibodies for neuronal specific nuclear protein (NeuN), microtubule-associated protein-2 (MAP-2) and cysteinyl aspartate specific proteinase 3 (Caspase-3). Results The number of Nissl body and NeuN-positive cells were increased significantly in the cortex region of LIG treatment group compared with those in the model group (P<0.01). The number of Caspase-3 positive cells in rat cortex region was decreased significantly in LIG treatment group compared with that in the model group (P<0.01). LIG treatment also improved the MAP-2 positive structures in the cortex region compared with the model group. Conclusion LIG may have neuron protective effects on cortex regions of cerebral hypoperfusion rats through reducing apoptosis of hypoperfusion rat cortical neurons and regulating the expression of MAP2.