Background and aim of the work: Acetaminophen is considered the most popular used over-the-counter (OTC) pain killer taken during pregnancy. Because of the scanty information regarding the safety profile of this drug during pregnancy This study was conducted to estimate the effect of acetaminophen on the ovary of adult pregnant albino rats and its effect on the offspring. Material and Methods: Forty adult female rats twenty mothers weighing (180-220 gm) and twenty female offspring weighing (5-10 gm), divided into four groups; the 1st Group (control mothers), 2nd Group (acetaminophen treated mothers), 3rd Group (offspring of the control mothers) and 4th Group (treated mothers' offspring). After 75 days of delivery, blood samples and ovarian sections were taken for assessment of ovarian structure. Results: The control mother and their offspring group compared to treated mothers group and their offspring showed a decrease in the serum level estradiol, an increased FSH serum level with considerable structural changes, including multiple atretic follicles with a degeneration in its oocytes also there was increased collagen fibers deposition in the medulla and ovarian stroma with a defective carbohydrate metabolism. Conclusion: Acetaminophen affect female fertility by disturbing ovarian architecture, increase collagen deposition and affect carbohydrate metabolism in the ovary.