Introduction: Humans are constantly subjected to different stressors that endanger their ability to live a normal life. Since the adrenal gland is the primary organ implicated in the stress response, the purpose of this study was to assess the effects of stress on this organ and the contribution of ibuprofen and Mesenchymal stem cells microvesicles to ameliorate these effects. Materials and Methods: Four groups of ten rats each: control group, stress group that subjected to various forms of stress for two weeks Ibuprofen group received an intraperitoneal injection of 60 mg/kg ibuprofen after the stress period. MSC-MVs group received a single intravenous injection of 15 ul of MSC-MVs in 0.5 ml PBS after the stress. The rats then were sacrificed and adrenal gland samples were prepared for immunohistochemical staining and light microscopy. Blood samples was taken for analysis of cortisol, aldosterone, malondialdehyde, and interleukin-6 levels. Results: Sections stained with H&E and immunohistochemical stains showed a mild improvement in ibuprofen group. The biochemical results confirmed that MSC-MVs group results were equivalent to those of the control group at the same period. There was no observable difference between the control group and MSC-MVs group. Conclusion: When given chronically and simultaneously under stressful settings to male albino rats, MSCs-MVs improves the histological alterations of the adrenal gland. Ibuprofen also helps these modifications, but to a lesser extent.