International Journal of Zoological Research1811-97781811-9786Academic Journals Inc.10.3923/ijzr.2017.64.73HajamYounis Ahmad RaiSeema RoyAnkita BasheerMuddasir GhoshHindole 22017132Background and Objective: Diabetes is one of the foremost culprit responsible in degrading the health of a person in this stressful life. The present study focused on protective effect of melatonin (MEL) on brain of streptozotocin (STZ) induced diabetic rat. Materials and Methods: Thirty six male rats were randomly divided into six groups, each group contain six rats, Control, STZ induced, STZ+Mel, Mel, STZ+GB (Glibenclamide) and GB. Streptozotocin was injected for six days continuously thereafter blood glucose level were censored after 72 h. The animals showing blood glucose level above 250 mg dL1 were considered as diabetic and were administered with exogenous Mel for 4 weeks. Animals were euthanized after 4 weeks. Brain of all respective groups were dissected, weighed and fixed in Bouins fixative for histological studies as well as processed for the assessment of biochemical variables viz lipid peroxidation (LPO), antioxidative defense system; reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activity and total protein quantification. Data were analyzed by students t-test followed by one-way ANOVA to compare between different experimental groups. Results: Streptozotocin (STZ)-induced diabetic rats exhibited significant increase in rate of LPO (p<0.001) but a significant decrease in organ weight, GSH, SOD, CAT and total protein content (p<0.05, 0.01 and 0.001). However, melatonin treatment restored LPO, weight of brain, total protein, catalase (CAT) SOD, GSH (p<0.05, 0.01 and 0.001). Decrement in hippocampal volume signifies the brain cell damaged might have resulted due to increased free radical load during diabetes. 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