Objective To investigate the effects of surgical trauma on Toll-like receptor 4(TLR4)expression in the hippocampus of aged mice. Methods Ninety male Kunming mice, aged 16-18 months, weighing 30-40 g, were randomly divided into 3 groups(n=30 each)using a random number table: control group(group C), anesthesia group(group A), and partial hepatectomy group(group PH). Normal saline 0.1 ml/10 g was injected intraperitoneally in group C. In group A, fentanyl 0.2 mg/kg and droperidol 5 mg/kg were injected intraperitoneally.In group PH, fentanyl 0.2 mg/kg and droperidol 5 mg/kg were injected intraperitoneally, and the mice underwent partial hepatectomy.Cognitive function was assessed using Morris water maze test at 1, 3, and 7 days after anesthesia or surgery.After the end of the test, the hippocampus was immediately harvested for determination of the TLR4, tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)protein and mRNA expression by Western blot and real-time reverse transcriptase-polymerase chain reaction, respectively. Results Compared with group C, no significant changes were found in group PH in the escape latency, percentage of swimming distance in the target quadrant, and TLR4, TNF-α and IL-1β protein and mRNA expression at each time point after anesthesia in group A(P>0.05), and the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF-α and IL-1β protein and mRNA was up-regulated at 1 and 3 days after surgery in group PH(P<0.05 or 0.01). Compared with group A, the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF-α and IL-1β protein and mRNA was up-regulated at 1 and 3 days after surgery in group PH(P<0.05 or 0.01). Conclusion Surgical trauma can up-regulate the expression of TLR4 in the hippocampus of aged mice, which may be involved in the mechanism of surgical trauma-induced postoperative cognitive dysfunction. Key words: Surgical procedures, operative; Cognition disorders; Aged; Toll-like receptor 4