Although the expression of cyclooxygenase-2 (COX-2) is closely associated with inflammation in the brain, it is constitutively expressed in the brain, and its expression is regulated by synaptic activity. The present study investigated postnatal expression of COX‑2 in the hippocampus in C57BL/6 mice at postnatal days (P) 1, 7, 14, 28, and 56. In addition, the presented study examined the effects of COX‑2 on synaptic plasticity through Arc, phosphorylated cAMP response element‑binding protein (pCREB), N‑methyl‑d‑aspartate receptor 1 (GluN1), and GluN2A/2B immunohistochemistry, which was performed on COX‑2 knockout (KO) and wild‑type (WT) mice. Extremely weak COX‑2 immunoreactivity was detected in the hippocampal CA1‑3 areas in addition to the dentate gyrus at P1. Conversely, COX‑2 immunoreactivity was observed in the stratum pyramidale of the CA1‑3 regions and in the outer granule cell layer of the dentate gyrus at P7. Additionally, although peak COX‑2 immunoreactivity was observed in all hippocampal sub‑regions, including the dentate gyrus at P14, it was significantly decreased at P14. Finally, COX‑2 immunoreactivity and the distribution pattern seen at P56 in the hippocampal CA1‑3 regions were similar to those observed at P28, whereas, they were identified in the inner half of the granule cell layer of the dentate gyrus. The western blot analysis revealed that the COX‑2 protein levels peaked at P14 and were decreased at P28 and P56. Additionally, the number of Arc and pCREB immunoreactive cells as well as GluN1 and GluN2A/2B immunoreactivity of COX‑2 KO mice were significantly decreased in the dentate gyrus when compared with that in WT mice. Taken together, the results of the present study suggest that COX‑2 serves an important role in synaptic plasticity in the dentate gyrus and changes in the levels of its constitutive expression are associated with the hippocampal dentate gyrus postnatal development.