Background C-C motif chemokine ligand 2 (CCL2) is reported to be involved in the pathogenesis of various neurological and/or psychiatric diseases. Tissue or cellular expression of CCL2, in normal or pathological condition, may play an essential role in recruiting monocytes or macrophages into targeted organs, and be involved in a certain pathogenic mechanism. However, few studies focused on tissue and cellular distribution of the CCL2 peptide in brain grey and white matters (GM, WM), and the changes of the GM and WM cellular CCL2 level in septic or endotoxic encephalopathy was not explored. Hence, the CCL2 cellular distribution in the front brain cortex and the corpus callosum (CC) was investigated in the present work by using immunofluorescent staining. Results (1) CCL2 like immunoreactivity (CCL2-ir) in the CC is evidently higher than the cortex. When the measurement includes ependymal layer attached to the CC, CCL2-ir intensity is significantly higher than cortex. (2) Structures in perivascular areas, most of them are GFAP positive, contribute major CCL2-ir positive profiles in both GM and WM, but apparently more in the CC, where they are bilaterally distributed in the lateral CC between the cingulate cortex and ventricles. (3) The neuron-like CCL2-ir positive cells in cortex are significantly more than in the CC, and that number is significantly increased in the cortex following systemic lipopolysaccharide (LPS), but not in the CC. (4) In addition to CCL2-ir positive perivascular rings, more CCL2-ir filled cashew shape elements are observed, probably inside of microvasculature, especially in the CC following systemic LPS. (5) Few macrophage/microglia marker-Iba-1 and CCL2-ir co-labeled structures especially the soma is found in normal cortex and CC; the co-localizations are significantly augmented following systemic LPS, and co-labeled amoeba like somata are presented. (6) CCL2-ir and astrocyte marker GFAP or Iba-1 double labeled structures are also observed within the ependymal layer. No accumulation of neutrophils was detected. Conclusion There exist differences in the cellular distribution of the CCL2 peptide in frontal cortex GM and subcortical WM-CC, in both the physiological condition and experimental endotoxemia. Which might cause different pathological change in the GM and WM.