Postoperative cognitive dysfunction is a common neurological complication, characterized by impaired learning and memory, that occurs after anesthesia and surgery, especially in elderly patients. The traditional Chinese medicine baicalin is known to have neuroprotective effects. Therefore, we have investigated whether baicalin can improve postoperative cognitive impairment in aged rats after splenectomy. A total of 60 Sprague Dawley rats were randomly divided, equally, into the splenectomy, sham operation (Sham), low-dose baicalin (Baicalin A), medium-dose baicalin (Baicalin B), and high-dose baicalin (Baicalin C) groups. Splenectomy was performed under anesthesia in all groups except for the Sham group, in which an appropriate concentration of saline was administered. The effects of baicalin on learning and memory were examined by the Y-maze behavioral experiments. Although splenectomy had a negative effect on cognitive function in the acute phase, all the rats spontaneously recovered on a postoperative day seven. Nonetheless, in the acute phase, the medium and high doses of baicalin slightly alleviated these effects of the procedure. The protein expression of the inflammatory cytokines tumor necrosis factor- \alpha , Interleukin-6, and Interleukin-1 \beta was assessed using enzyme-linked immunosorbent assay. Their levels were elevated in the acute phase but were returned to normal with the medium and high dose of baicalin. Real-time PCR analysis of the mRNA expression of the N-methyl-D-aspartic acid receptor TNF- \alpha , which is known to be involved in long-term potentiation, revealed that baicalin promoted its transcription. Thus, the findings indicate that baicalin may improve postoperative cognitive memory dysfunction in postoperative cognitive dysfunction in rats via anti-inflammatory mechanisms and pathways that involve N-methyl-D-aspartate receptor 2B subunit.