Introduction: Numerous evidence indicates the involvement of Insulin and K ATP channel blockers in brain functions such as memory. Materials & Methods: In this study, by applying light (H & E staining) and scanning electron microscopies, we investigated the effect of intrahippocampal injection of insulin, glibenclamide experimental diabetic rats. May these reverse the cellularimpairment, and prevent neural damage in hippocampus. In this study male rats were undergone stereotaxic surgery and cannulation, they subjected to intrahippocampal injection of insulin, glibenclamide, insulin and glybenclamide, vehicle, and saline. Average size of cell bodies and average number of denderitic spines per 10 micrometerwere recorded and analyzed. Resultes: The findings suggest that: (1) Insulin selectively influence pathological mechanisms in hippocampus. (2) Insulin and Glibenclamide protect hippocmpal neuronsagainst damage and preserve synaptic spines. Conculusion: We concluded that in Diabetic rates, insulin, glibenclamide and both have a benefitial effect on preventing damage and loss of hippocampal neurones and synaptic spines.