Postoperative cognitive dysfunction (POCD) is common in elderly patients, and may persist or even evolve into Alzheimer's disease. It has been hypothesized that POCD is mediated by surgery-induced inflammatory processes. As a pro-inflammatory cytokine, the detailed role of interleukin (IL)-6 in POCD remains largely unknown. In this study, laparotomy was used to mimic human abdominal surgery in aged Sprague-Dawley rats. It was found that memory and learning were impaired following surgery, accompanied by the significant upregulation of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-4, and IL-6. Moreover, the intracisternal administration of the IL-6 receptor (IL-6R) antagonist (tocilizumab, also know as MRA) at the time of surgery notably attenuated the surgery-induced cognitive deficit, and significantly inhibited the upregulated expression of pro-inflammatory cytokines. Further investigation indicated that the intracisternal administration of MRA inhibited the activation of the NF-kappa B signaling pathway in aged rats following surgery. In summary, the findings of this study suggest that IL-6 plays a crucial role in POCD, and that IL-6R antagonists may serve as novel agents for the prevention or treatment of POCD.