Background: Tributyltin is widely used as antifouling paint for marine vessels. It is slowly released from the paint to the water and becomes incorporated into soil, animals and plants. TBT has been identified as an endocrine disruptor and induces oxidative damage. Objectives: This study aimed to investigate the probable toxic effect of tributyltin on adrenal cortical cells of adult male albino rats for two different durations. Materials and Methods: Twenty four adult male albino rats were divided into 3 equal groups: Group I: was the control group; Group II: each rat received tributyltin orally at a dose of 1mg daily for one week. Group III: received the same daily dose for successive two weeks. At the end of the experiment, the animals were sacrificed and blood samples were subjected to hormonal assay for aldosterone, corticosterone and ACTH levels. Serum tin levels were assessed. The adrenal tissue was processed for light and electron microscopic examination. In addition, immunoreaction for CD 44 positive was performed. Results: A significant decrease in aldosterone and corticosterone, an increase in ACTH levels and an increase in the mean count of CD44 positive cells in group III have been revealed when compared with the other groups. Histological changes in group II were shown in zona glomerulosa and fasciculata in the form of loss of architecture, cytoplasmic vacuolation and disrupted mitochondrial cristae. Meanwhile, Group III showed few lipid droplets and deeply stained nuclei in both zones. Conclusion: Tributyltin has deleterious effects on cells of zona glomerulosa and zona fasciculata of the adrenal cortex of adult male albino rats which were time-dependent.