Clinical studies on cancer patients have revealed that chemotherapy is associated with long-term cognitive impairment. In the present study, we used a rat model to evaluate the effects of the anticancer drug cytosine arabinoside (Ara-C) on spatial learning, memory, and the dendritic morphology of neurons in the anterior cingulate cortex (ACC) and hippocampus. The drug was observed to induce deficits in the long-term spatial memory function but not in the spatial learning and recent memory, as was assessed by performing the Morris water maze test. In the Ara-C treated rats, retraction of the apical dendrites was noted in the neurons in the ACC but not in the pyramidal neurons in the hippocampal region CA1. Our in vivo adult rat model of neurotoxicity provides data on the long-term cognitive and cellular morphometric alterations in the frontal lobes induced by Ara-C treatment. Retraction of the apical dendrites of the pyramidal neurons in the ACC may contribute to the remote spatial memory impairment induced by Ara-C treatment.