Background: Cognitive impairments are common finding with aging particularly in postmenopausal women. Dentate gyrus is the most specialized region in the hippocampus being involved in formation of new memories and neurogenesis. Panax Ginseng is a promising natural compound having many beneficial effects, including anti-inflammatory, antioxidant, antiaging activities. The aim of the current study was to explore the effect of ovariectomy on structure of dentate gyrus and the possible protective role of Panax Ginseng. Materials and methods: 25 adult female Albino rats were divided into three groups control group subdivided into 3 subgroups, ovariectomized (OVX) group and OVX plus Ginseng treated group. Hippocampal sections were subjected to biochemical, histological morphometric and immunohistochemical studies.Results: ovariectomized rats showed significant increase in their weight and decrease in serum estradiol level. Significant increase in malondialdehyde (MDA) with significant decrease in reduced glutathione (GSH) and catalase. Dentate gyrus of ovariectomized rats showed degeneration of granular layer with significant decrease in its thickness. Significant increase in expression of caspase-3, inducible nitric oxide synthase( iNOS), Glial fibrillary acidic protein (GFAP), and significant decrease in , Microtubule-Associated Protein (MAP2),synaptophysin and Ki 67 immunoreactivity were detected. Treatment of ovariectomized rats with Panax Ginseng induced significant reduction in weight and MDA with significant increase in estradiol level, GSH and catalase. Significant decrease in expression of caspase-3, (iNOS), (GFAP) and increase (MAP2), synaptophysin and Ki 67 expression with improvement of the histopathological changes. In conclusion, Panax Ginseng may serve as a promising therapeutic substitute in amelioration of menopausal related cognitive affection.