Royal jelly (RJ) is a honey bee secretion with numerous medicinal properties and antioxidant activities. Morphine is a major risk factor in the development of functional disorders in several organ systems. This study was designed to evaluate the effects of RJ against morphineinduced damage to the prefrontal cortex of rats. Materials and Methods: In this study, 48 male Wistar rats were randomly assigned into 6 groups: sham group, morphine group, RJ groups (100, and 200 mg/kg), and morphine + RJ

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... roups. Treatments were administered intraperitoneally and orally for 20 days on a daily basis. Ferric reducing/ antioxidant power (FRAP) method was applied to determine the total antioxidant capacity. The number of neurons and, dendritic spines were investigated by Golgi technique, and Griess technique was employed to determine the serum nitrite oxide level. Results: Morphine administration significantly increased the nitrite oxide level and total antioxidant capacity, and reduced neuronal dendritic spines and neurons compared to the sham group (P < 0.05). In all RJ and Morphine + RJ groups, the number of neurons and neuronal dendritic spines were elevated significantly, while nitrite oxide level and total antioxidant capacity were reduced compared to the morphine group (P < 0.05). Conclusions: RJ administration protected animals against oxidative stress and nitrite oxide. It also improves some prefrontal cortex parameters including number of neurons and dendritic spines because of the morphine.