The present study carried to investigate the toxic pathology effect of both bulk Al(OH) 3 and Al(OH) 3 nanoparticles materials. Also, to examined cerebral cortex-kb p65 expression level by immunohistochemistry test. The crystalline and grain size of nanoparticles and it is morphology are tested by XRD, AFM, SEM, and EDEX respectively. This study included 40 neonatal mice of both sexes were randomly divided into 7 groups. This group's immunized subcutaneously, two times, the first dose was at third postnatal, and the second dose was at 17 days postnatal. These groups classified as follows:-the 1st group of mice injected by normal saline which serves as control negative, while the 2nd group immunized by oval albumin which serves as control positive. The 3rd group immunized by bulk-Al(OH) 3 , the 4th group immunized by Al(OH). The Brain tissue samples were collected from each at 4 weeks and 8weeks post first immunization for histological examination. The Histopathological results of the 1st group, 2nd group do not show clear histopathological changes. Whereas, histopathological changes of the 3rd group was severe at 4 weeks post first immunization, while at 8 weeks post first immunization pathological changes were more severe. However, histopathology changes of the 4th group were less severe (moderate) in 4, 8 weeks post first immunization compared with the 3rd group. The immunohistochemical test results of the 3rd group show a highly significant increase (P < 0.05) (70.2%, 95.6 %) in 4, 8 weeks post first immunization. Whereas, the results of the immunohistochemical test of the 1stad 2nd group, show a significant difference (p<0.05) at 4, 8 weeks post first immunization. While the 4th group shows a significant difference (61%) (P<0.05) in 8 weeks post first immunization compared with Bulk-Al (OH) 3 . These results demonstrated the toxic effects of bulk Al (OH) 3 on the neonatal brain. This study suggested that the chitosan alone and presence with Al(OH) 3 in nanomaterial or bulk form safer and less toxic as an adjuvant.In conclusion, It could be concluded that repeated exposure of neonatal mice to Bulk-Al(OH) 3 induced histological alterations in various areas of the brain. In addition, results further showed that the expression of NF-κB p65 is significantly increased in the brain of Bulk-Al(OH) 3 mice when compared with the control groups. Results of mice immunized with Al(OH) 3 NPS severity of toxicity was less than bulk-Al(OH) 3 . Accordingly, it was concluded that Al adversely affected the brain by histological, immunohistochemical. These alterations are dangerous because of neonatal exposure to aluminum in life. Key word: Al (OH) 3 NPs,BulkAl(OH) 3 ,,Neonatal mice , NF-kb p65,histopathology How to cite this article: Al-Murshedy NAK, Fares BH (2020): Pathological effect of aluminum hydroxide compared with polymer-based nanoparticles on neonatal mice brain, Ann Trop Med &