Alzheimer's disease (AD), a degenerative disease of the central nervous system, is mainly treated by cholinesterase inhibitors and memantine. We aimed to assess the protective effects of resveratrol (RES) on hippocampal nerves in AD rats. Forty healthy Sprague-Dawley rats were assigned into model, blank, low-dose RES, and highdose RES groups (n = 10). After modeling, RES groups were daily injected with corresponding doses of RES. Their cognitive functions were tested on days 1, 5, 10, and 14. The cellular morphology was compared through hematoxylineosin staining. The levels of norepinephrine (NE), dopamine (DA), choline acetyltransferase (ChAT), malondialdehyde (MDA), nitric oxide (NO), reactive oxygen species (ROS), activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as total antioxidant capacity (TAOC) were detected. The expressions of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor E2-related factor 2 (Nrf2) were measured using Western blotting. Compared with model group, the escape latency, the balance beam score, the Longa score, and the levels of ROS, MDA, NO, and iNOS activity were significantly decreased in the RES groups (p < 0.05); while the platform-crossing times, the levels of NE, DA and ChAT, the activities of CAT, GSHPx and SOD, T-AOC and protein expressions of Nrf2 and Keap1 were significantly increased (p < 0.05). Hippocampal pathological changes were significantly relieved in the RES groups compared with those in the model group. RES exerts protective effects on hippocampal neurons, regulates the neurotransmitter level, and reduces oxidative stress response, probably by activating the Nrf2/ARE pathway. [ABSTRACT FROM AUTHOR]