Petroselinum crispum (P. Crispum) is an associate of the umbelliferae family with several therapeutic attributes. Morphine is known as a major risk factor in the development of functional disorder of several organs.This study was designed to evaluate the effects of P. Crispum extract against morphine-induced damage to the brain prefrontal cortex (PC) of rats.In this experimental study, 64 Wistar male rats were randomly assigned to 8 groups: Sham group, Morphine group, P. Crispum groups (50, 100, and 150 mg/kg), and Morphine + P. Crispum groups. Daily intraperitoneal treatment applied for 20 days. Ferric reducing/antioxidant power method was hired to determine the total antioxidant capacity (TAC). The number of dendritic spines was investigated by Golgi staining technique. Cresyl violet staining method was used to determine the number of neurons in the PC region. Furthermore, Griess technique was used to determine the level of serum nitrite oxide.Morphine administration increased nitrite oxide levels and decreased TAC, density of neuronal dendritic spines and neurons compared to the sham group significantly (P < 0.05). In whole doses of the P. Crispum and Morphine + P. Crispum groups, the number of neurons and neuronal dendritic spines increased significantly while nitrite oxide level and TAC decreased compared to the morphine group (P < 0.05).It seems that the administration of P. Crispum extract protects the animals against oxidative stress and nitrite oxide, also improves some PC parameters including the number of neurons, and dendritic spines because of the morphine application.