Objective. The aim of this study is to investigate the effect of dexmedetomidine on cognitive dysfunction and inflammatory cytokines in the hippocampus after surgery in aged rats. Methods. A total of 30 healthy male Sprague Dawley rats were divided into control group, sham group, and dexmedetomidine group. A splenectomy rat model was established and dexmedetomidine was intraperitoneally injected before operation. The cognitive function of rats was examined by Morris Water-Maze Test, open field experiment, and passive avoidance memory test. And the expression levels of IL-6, IL-1β, and TNF-α in the hippocampus were examined by ELISA. Results. The escape latency for 5 continuous days in dexmedetomidine group was significantly decreased comparing with control group (all P < 0.05 ). The number of times of swimming and the percentage of swimming time in dexmedetomidine group were significantly more than those in control group (all P < 0.05 ). What is more, rats in dexmedetomidine group had the decreased time of stay in the central square and the increased number of standing times in comparison with the control group, and the statistical differences were found (all P < 0.05 ). Compared with the control group, dexmedetomidine intraperitoneally injected before surgery could significantly inhibit the expression levels of IL-6, IL-1β, and TNF-α in the hippocampus, and there were statistical differences (all P < 0.05 ). Conclusion. Dexmedetomidine could significantly relieve the postoperative cognitive dysfunction in aged rats. The mechanism may be associated with the decreased inflammatory cytokines in the hippocampus.