Background: All-trans-retinoic acid (ATRA), an active metabolite of vitamin A, plays a significant role in controlling various physiological processes, including embryonic development and epithelial differentiation. ATRA is utilized as a chemotherapeutic agent for treating of acute promyelocytic leukemia (APL) in pediatric patients. Besides its efficacy in APL therapy, ATRA is extensively used in the treatment of various skin diseases such as psoriasis, skin cancer, acne, and ichthyosis. Aim: This study aimed to assess the impact of high-dose ATRA on tibial growth by measuring serum growth hormone “GH," histomorphometric measurements of tibia, and histopathological examination of tibia in young male albino rats. Methods: This experimental study included 54 male albino rats, aged 6 weeks, divided into three groups: group I and group II served as control groups, whereas group III was administered ATRA treatment (40 mg/kg/day of ATRA suspension administered via gavage, dissolved in 1 cc of corn oil at a concentration of 10 mg/ml, with an oral LD50 of 2 g/kg). Each group was subdivided into three subgroups, each comprising six rats. The research was submitted to the Research Ethics Committee of the Faculty of Medicine at Benha University. The study assessed the effects of ATRA treatment on serum growth hormone, weight, tibial length, nose-tail length, outer cortical bone thickness, relative bone resorption eroded surface percentage, osteoclast count, and osteoblast count compared to control groups. Results: There were no notable variations in these parameters among the control groups. In addition, there were no significant differences in osteoblast count among all groups. The ATRA-treated groups demonstrated a significant decrease in serum growth hormone, weight, tibial length, nose-tail length, and outer thickness of cortical bone, as well as a highly significant increase in relative bone resorption eroded surface percentage and osteoclast count. Conclusion: High-dose administration of ATRA resulted in a reduction in growth measurements, including weight, tibial length, and nose-tail length with histological alterations and histomorphometric changes.