Insulin is useful for the treatment of diabetes mellitus. Because of its high molecular weight, it is difficult to permeate through transdermal routes. There is no existing formulation available for the dermatologic manifestation of diabetes. Thus an attempt was made to prepare insulin-loaded microemulsion topical gel with aloe vera. The insulin-loaded microemulsion was prepared using 3 square factorial design, using oleic acid as oil phase, tween-80 as the surfactant and poly ethylene glycol-400 as co-surfactant. Physical stability studies performed and amongst all of them, the best three formulations selected for ex vivo insulin permeation study. The batch with the best permeation was selected to prepare the topical gel with and without aloe vera. Post evaluation parameters of topical gel with skin irritation study and in vivo study performed. In vivo study results revealed that the groups of diabetes Wistar albino rats with skin infections; by the treatment of topical gel of insulin-loaded microemulsion with aloe vera gel was found to reduce the blood glucose level and skin infection as compared to one without aloe vera gel. It was concluded that insulin loaded microemulsion topical gel with aloe vera can be used as dermatologic manifestation of diabetes significantly.