Authors reported that exposure to acetaminophen postnatally may be linked to increasing the risk of ASD. However, the reports on its effects on the brain are scanty, and the knowledge concerning their safety is little as there is a traditional left out of the clinical trials by users. The present work tried to elucidate the histological effects of acetaminophen on the hippocampus of neonate male rats after early postnatal exposure. The pups were categorized into2 groups, the control group, and the acetaminophen treated group. The acetaminophen treated animals were injected subcutaneously with acetaminophen of 60 mg/Kg/day from postnatal day (PND) 7 to PND 14, while the control group treated with normal saline with a similar approach. The histopathologic assessment revealed a diminishing in the pyramidal cells layer thickness of Cornue Ammonis. Some areas are devoid of cells with the appearance of Ghost like cells indicating features of neural cell death, degenerated neurons in the pyramidal layer are noticed. Features of nuclear clumping of pyramidal cell layer were shown. Moreover, several changes including vacuolations in the granular layer of DG with disorganization in DG. Neuronal processes presented with clumping. Apoptosis in the granular cells layer and hilus of a section of DG with the appearance of many astrocytes and microglial cells. Exposures to clinically relevant doses of acetaminophen in the postnatal period were shown to affect the histology of rat hippocampal regions, and a balanced risk assessment based on the best professional judgment must be prioritized.