Background:Aspartame is widely consumed worldwide. Its metabolites can be toxic to various body organs. L-Arginineis widely available in daily food products and it has an antioxidant property. Aim:This study was done to evaluate the protective effect of L-arginine on aspartame treated adrenal gland in a rat model using histological, immunohistochemical, biochemical, and morphometric studies. Material and Methods: Fifty adult male albino rats five-sixmonthold, weighing180-200 grams were used. They were divided into five groups. Group I(Control). Group II(L-arginine): each rat received 0.3mg/ gm/dayfor 4 weeks. Group III (Aspartame group): each rat received 250mg/Kg/day for 4 weeks. Group IV (Aspartame+L-arginine treated group) each rat received L-arginine & aspartame as in groups II & III respectively.  Group V (Recovery group): each rat received aspartame as in group III, then, rats were left for another 4 weeksbefore they were sacrificed. Adrenal glands were dissected and subjected to Hematoxylin&Eosin andMasson's Trichromestains, Caspase-3, biochemical and morphometric studies.  Results: In aspartame group, the adrenal cortex revealed decreased capsular thicknesswith complete shedding in some areas byMasson's Trichrome,disorganization of the cellular arrangement in adrenal cortex.Some cells revealed vacuolated cytoplasm, others appeared with pyknotic nuclei by Hematoxylin&Eosin.ACTH, cortisol, aldosterone, and MDA concentrations were significantly increased while GSH concentration was significantly decreased in aspartame group. Aspartame group showed significant increase in positive immunoreactivity for Caspase-3, compared to other groups. L-arginine treatment improved the histological, immunohistochemical, biochemical, and morphometric results. Recovery group (V) revealed incomplete improvement.  Conclusion: L-arginineprotects the adrenal cortex from the aspartame induced toxicity inadult male albino rats.