Demyelination is a pathological process characterized by myelin loss from around axons, while remyelination is the repair response through the restoration of myelin and the resolution of functional deficits. Multiple sclerosis is a high-incidence inflammatory demyelinating disease in which remyelination frequently fails. IMT504 (IMT) is a non-CpG oligodeoxynucleotide consisting of 24 nucleotides and characterized by 2 specific PyNTTTTGT sequences. On the basis of IMT immunomodulatory effects and regenerative properties, and our previous results showing its beneficial effects on neuroinflammation and remyelination in the corpus callosum of cuprizone (CPZ)-demyelinated rats, this work aims to study IMT role in microglial and oligodendrocyte (OL) lineage cell populations in the cerebral cortex (Ctx). We subcutaneously administered IMT every day for five days before CPZ withdrawal. Brain samples were then analyzed 0 (T0), 3 (T3), 7 (T7) and 10 (T10) days after CPZ withdrawal. Immunohistochemical results show that IMT did not change the population of Iba1+ microglial cells per area or APC+/Sox10+ OLs at any of the times analyzed. However, IMT produced a significant increase in PDGFRα+ OL progenitor cells at T3 and in MAG+ mature OLs at T7 as compared to CPZ-treated rats injected with saline solution. These findings support potentially beneficial properties of IMT in the myelin repair process of demyelinated Ctx lesions.