Background: One of the popular painkillers, paracetamol is thought to be safe for use in pregnant women, and nursing mothers.
Objectives: To observe the effect of paracetamol on the development of the medial prefrontal cortex (mPFC) in albino rats and to evaluate the protective effect of silymarin.
Material and Methods: Forty pregnant rats were divided randomly into four equal groups: Group A:  received nothing. Group B:  was given silymarin at a dose of 200 mg/kg body weight orally once daily. Group C: was given paracetamol at a dose of 350 mg/kg body weight orally once dailly. Group D: was given paracetamol and silymarin. Treatment started at the sixth day of the gestation until the end of lactation. After weaning, the pups received the same regimen until the age of three months. The offspring were selected from each group at the following ages: 1 day, 21 days and 3 months The mPFC was processed for light, ultrastructural and immunohistochemical analyses.
Results: Paracetamol exposure led to  hypocellularity in different layers of mPFC, shrunken pyramidal neurons, vacuolated neuropil, weak SYN immunoreaction and a decrease in the number of pyramidal cells and thickness of the mPFC. Silymarin coadministration induced a partial restoration of normal arrangement of the mPFC, the cytoarchitecture of pyramidal neurons, SYN immunoreaction as well as an increase in the number of the pyramidal cells and  thickness of the mPFC.
Conclusion: Paracetamol treatment caused neuronal damage in the mPFC. Silymarin appeared to be beneficial in protecting mPFCʼ structure.