Introduction: Kainic Acid (KA) is an ionotropic glutamate receptor agonist. KA can induce neuronal overactivity and excitotoxicity. Rosmarinic Acid (RA) is a natural polyphenolic compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory properties. This study aimed to assess the effect of RA on apoptosis, nNOS-positive neurons number, as well as Mitogen-Activated Protein Kinase (MAPK) and Cyclooxygenase-2 (COX-2) immunoreactivity, following intrahippocampal Kainic acid injection in rats. 
Methods: The study rats were randomly assigned to three groups of sham, KA (KA was injected into the right side of the hippocampus) and KA+RA (a dose of 10 mg/kg/day through a gavage needle for one week before KA injection). Then, histopathological changes, including apoptosis [Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay], nNOS-positive neurons number, as well as COX-2 and MAPK immunoreactivity were evaluated in the hippocampus. 
Results: In the RA pretreated group, nNOS-positive neurons and TUNEL- positive cells were significantly reduced compared to the KA group (P<0.05). COX-2and MAPK immunoreactivity demonstrated no significant changes compared to the KA group. They indicated a significant higher reactivity for COX-2 (P<0.01) and MAPK (P<0.005) versus the sham group. 
Conclusion: RA had neuroprotective effects, compared to KA, through reduced apoptosis and nNOS-positive neurons, but not MAPK and COX-2.