Introduction: Studies have shown that even acute single dose of ketamine is associated with neurodegeneration in hippocampus. The aim of this study was to examine the effects of chronic exposure to ketamine on hippocampus proper in young adult male rats. Materials and Method: Twenty young adult male wistar rats weighing 120-150 g were randomly divided into two groups. Experimental group received ketamine intraperitoneally at the dose of 10mg/kg for one week. The control animals only received saline. At the end of week animals were anesthetized and the hippocampus and adrenal were harvested for further study. Results: Cytological examination of cresyl violet stained sections of ketamine group showed dark neurons in CA4 region. The number of dark neurons in CA4 (15±3) showed meaningful difference with control (P<0.001). The weight of wet brain in ketamine group (1.34±0.04 gr) showed significant level of difference in comparison with those of control (1.6±.2gr) (P<0.05). The presence of oligodendrocytes aggregation around degenerating and healthy looking neurons was only recognized in ketamine group. Also in ketamine exposed animals, hypertrophic astrocytes especially in white matter hilar region, were observed. Conclusion: According to our findings it could be concluded repeated or chronic ketamine use is associated neurodegeneration in CA4region of hippocampus and sever glial reaction.