Tributyltin (TBT), a persistent environmental pollutant used in antifouling paints, agricultural fungicide, and wood preservatives, induces adrenal toxicity. This study evaluated adrenal cortex recovery following TBT exposure and the role of HMGB-1 (High Mobility Group Box-1), Beclin-1, and nuclear factor kappa B (NF-κB) in these effects. Eighteen male rats were equally allocated to 3 groups: Control (n = 6; corn oil vehicle gavage), TBT-treated (n = 6; 5 mg/kg tributyltin chloride (TBTC) by gavage for 8 weeks), and recovery (n = 6; TBTC for 8 weeks followed by 4 weeks washout). Serum hormones (aldosterone, corticosterone, DHEAS (dehydroepiandrosterone sulphate), and ACTH (adrenocorticotropic hormone), oxidative stress markers, histopathology, ultrastructure, and immunohistochemistry were assessed. TBT significantly disrupted adrenocortical function, reducing serum aldosterone, ACTH, and DHEAS while elevating corticosterone. Adrenal oxidative stress increased, evidenced by elevated MDA and reduced SOD (superoxide dismutase), and GPx (glutathione peroxidase). Histopathology revealed cortical zonation disruption, vacuolation, and hemorrhage. Electron microscopy showed nuclear abnormalities, mitochondrial shrinkage, and lipid droplet proliferation. Immunohistochemistry demonstrated upregulated HMGB-1, Beclin-1 (autophagic marker), and NF-κB indicating DAMPs (Damage-Associated Molecular Patterns) release, autophagic activation, and inflammatory signaling. A 4-week recovery period partially reversed these changes; hormonal level improved, oxidative stress lessened, cortical architecture partially restored, lipid accumulation reduced, and marker expression declined, though residual vacuolation and congestion preserved. In conclusion, TBT induces reversible adrenocortical toxicity mediated by oxidative stress, HMGB-1/ NF-κB signaling, and autophagy, with incomplete recovery after 4 weeks.