Background: Diclofenac sodium (DS) can induce developmental abnormalities in embryos if consumed during pregnancy.. Objective: To assess the effect of prenatal administration of therapeutic dose of DS during the critical period of organogenesis on development of different neonatal organs of albino rats and on maternal organs, as well as to spotlight on the immunohistochemical reactions that may explain the possible impacts of DS. Material and Methods: After mating, 18 pregnant rats were allocated into three groups. Group (I): received balanced diet, Group (II): received intraperitoneal injection (IP) of 1mL/kg/day of distilled water, Group (III): received IP of 1.5mg/Kg.bw/day of DS dissolved in distilled water from 7th -14th days of gestation. The mothers (6/group) and their newborns (10/group) were anaesthetized following labor. The placentae and livers from mothers and hearts, livers, and lungs from their neonates were examined after preparation using light microscopy immunohistochemical, morphometric studies and statistical analysis Results: Histologically, in all DS-treated groups, there was degenerative histopathological changes in the organs of both pregnant albino rats and their neonates. Morphometric and statistical analysis showed highly significant increase in the area percentages of positive TNF-α and iNOS immunoreactions in all DStreated groups as compared to their control groups. Moreover, the most affected organ in mothers was the placenta while, the lung tissues in neonates. Conclusion: The current investigation found that giving therapeutic doses of DS during the period of organogenesis caused significant histopathological alterations in both maternal and neonatal organs enhanced by upregulation of proinflammatory markers linked to oxidative stress.