Background: Buspirone hydrochloride (Buspar) belongs to the azapirone family which is primary used to treat anxiety during pregnancy. Buspar is considered to be the safest anxiolytic drug to use during pregnancy. This work studies the effect of Buspirone hydrochloride on fetal pancreas and the postulated role of selenium to reduce the adverse effects of the drug. Aim of the work: The aim of this work is to investigate the destructive effect of buspirone on the fetus pancreas and the possible antagonistic effect of selenium. Material and methods: buspirone hydrochloride tablets were obtained from Beecham pharmaceutical, Cairo, Egypt. Eighty-one albino rats were used throughout the study,  54 female and 27 males. The rats were assigned into three groups eighteen female albino rats with nine male albino rats. Group I: In this group, received  water only. Group II: In this group, pregnant rats were given oral doses of buspirone at a dosage of 4.1mg/kg/day, from the 6th day to the 20th day of pregnancy. Group III: In this group, the pregnant rats were given oral buspirone at a dose of 4.1 mg/kg/day from the 6th to the 20th day of conception, with oral selenium at a dosage of 0.3mg/kg/day. Fetuses were collected and the pancreases were harvested for histological, and immunohistochemical analyses. Results: Buspirone induced marked histopathological changes fetal pancreases which was remarkably ameliorated by the prophylactic use of Selenium. Conclusion: This work revealed a prophylactic role for selenium in uspirone induced fetal pancreatic damage. Thus, selenium administration to patients on buspirone is recommended during pregnancies to avoid offspring pancreatic damage