Abstract Dentate gyrus is a fundamental sub-region of the hippocampus which is directly engaged in higher memory and cognitive functions. This study was performed to describe the histological and immunohistochemical changes in dentate gyrus in experimental animals during postnatal development. Forty four male albino rats were classified into four equal groups: new born group aged one day, adult group aged 3–6 months, early senile group aged 18–20 months and late senile group aged 30–31 months. Specimens of hippocampus were processed and prepared for routine hematoxylin and eosin stains and immunohistochemical expressions of calretinin, glial fibrillary acidic protein and Ki67 (Kiel 67). Morphometric data were statistically analyzed. The present results showed significant reduction in thickness of granule cell layer of late senile group. Interestingly, the mean number of immature neurons was significantly increased in early senile group, while it was significantly reduced in late senile group. The number of mature granule cells showed marked reduction in both early and late senile groups. Furthermore, the number of astrocytes and optical density of glial fibrillary acidic protein revealed significant age-dependent increase. Measurable difference in number of calretinin positive interneurons was detected between adult and senile groups. However, mean number of Ki67 immune positive nuclei expressed significant age-dependent reduction. This study concluded that interneurons play a substantial role in modulating dentate gyrus neurogenesis which occurs throughout life and steadily decreases during aging. It is recommended to focus on the different stimuli and factors that potentiate neurogenesis to prevent or treat cognitive deficiencies associated with aging.