Whether endogenous deficiency of adrenal corticosteroid by unilateral adrenalectomy leads to any modulation of macrophage response is not clear and needs investigation in detail. We performed unilateral adrenalectomy on male Swiss albino rats. Fractions of splenic macrophages were isolated and their functional activities were determined. To test the effect of adrenal hormone insufficiency (after unilateral adrenalectomy) on the cell mediated and humoral immune response, sheep red blood cells were injected, then the delayed type hypersensitivity (DTH) response and the number of antibody secreting plasma cells were determined. Studies reported herein indicate that in vivo glucocorticoid (GC) insufficiency due to unilateral adrenalectomy decreases chemotactic migration, myeloperoxidase enzyme release, and lysozyme release from rat splenic macrophages that were also related to the induction of cell mediated and humoral immune responses. The maximum number of plaque was obtained from control cells isolated from spleen after 10 days from the control rats, whereas the number of plaque was decreased in spleens isolated 20 days after unilateral adrenalectomy. Our study also showed time dependent decrease in foot pad swelling in the unilaterally adrenalectomized rats where endogenous GC was reduced with respect to control indicating reduced DTH response in case of GC insufficiency. We found slower clearance of bacterial burden from the blood and spleen isolated from unilaterally adrenalectomized rats with respect to control. Thus on one hand partially GC insufficient animals show altered macrophage response and on the other hand it heightens the persistence (in vivo) of Staphylococus aureus. The study may be helpful in understanding that adrenal corticosteroid insufficiency due to adrenalectomy interferes with immune functions, which may also support the hypothesis that endogenous GC plays a role in regulating immune response. © 2006 Elsevier GmbH. All rights reserved.