Undeniable evidence shows that microglia in the spinal cord undergo marked reactions following peripheral injuries. However, only rare studies have investigated the possible short and long term microglial reaction in brain regions following peripheral nerve injury and its interspecies specificities. In the present study we examined microglia in subdivisions of the prefrontal cortex in mice and rats, 7days and 42days after spared nerve injury (SNI) of the sciatic nerve. We show that a bilateral increase of microglial density takes place in the infralimbic cortex in rats 7days post-injury (sham vs. SNI, n=5: ipsilateral 35.4% increase of the median, p=0.0317; contralateral 24.9% increase of the median, p=0.0079), without any detectable change in the other investigated regions, namely the anterior cingulate, prelimbic and agranular insular cortices. In mice, no observable difference could be found in any region at both time points, neither using Iba-1 immunostaining nor with CX3CR1-eGFP animals. Our results indicate that a transitory, species-specific and highly regionalized microglial reaction takes place in the prefrontal cortex following peripheral nerve injury.