Midazolam is a member of the benzodiazepine group of tranquilizers. The present study aimed to investigate the histological and ultrastructural alterations induced by administration of midazolam on the adrenal cortex of male albino mice. Twenty adult male CD-1 mice were used in the present study. They were divided into two even groups. The first group served as control. The second group received daily double the therapeutic dose (0.26 mg/kg b.wt.) of midazolam for 28 days. The animals were sacrificed and adrenal samples were obtained and processed for histological and ultrastructural examination. Histologically, adrenal cortex sections of midazolam-treated mice revealed cytoplasmic vacuolation of the cells of three cortical zones; zona glomerulosa, fasiculata and reticularis, beside the nuclei of some of these cells showing signs of pyknosis, karyorrhexis and karyolysis. Ultrastructurally, cortical cells of midazolam-treated mice revealed conspicuous alterations, represented by deformed mitochondria with abnormal type of cristae (i.e. lamelliform). Besides, the rough endoplasmic reticulum was fragmented into small stacks and the smooth endoplasmic reticulum was dilated. The vacuolated cytoplasm contained numerous lysosomes, in addition to numerous lipid droplets. The nuclei showed clear signs of pyknosis and possessed irregular nuclear envelopes. In conclusion, it seems that the destructive impacts of midazolam on the adrenocortical cells reflected on their functions leading to much deficiency in their performance. So, it should be taken in the consideration and great concern that much drug must be utilized under restricted precaution in the medical fields to protect the human health from its hazardous impact.

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