Objective To investigate the effect of ulinastatin (UTI) on long-term learning and memory function after partial hepatectomy (PH) in mice. Methods Forty-five adult male specific pathogen free (SPF) C57BL/6J mice were randomly divided into control group (C group), PH group and UTI group (n=15 each). After the mice regained consciousness after operation, animals received intraperitoneally UTI at a dose of 50 000 U/(kg·day) for 30 consecutive days in UTI group. Animals were given intraperitoneally with the same volume of normal saline for 30 consecutive days in C group and PH group. The mice of the three groups underwent Morris water maze test at 24 h after the last pretreatment. The mice were euthanized after the test of learning and memory function, and hippocampi tissue was immediately excised for determination of wet weight to dry weight (W/D) and total water content (TWC). The expression levels of CCAAT enhancer-binding proteins homologous protein (CHOP) mRNA and protein of hippocampi tissue were detected respectively by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Apoptosis index (AI) of hippocampi tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Results Compared to C group [(17.39±7.72) s, (12.59±6.69) s; (2 122.57±543.48) mm, (1 123.69±369.32) mm], the escape latency [(54.48±9.69) s, (56.63±7.74) s] and swimming distance [(4 789.48±677.67) mm, (4 987.72±884.53) mm] were significantly prolonged (both P<0.05), W/D (5.47±0.98 vs. 2.79±0.78), TWC (4.43±0.97 vs. 1.79±0.72) and AI [(36.32±2.62)% vs. (2.69±0.75)%] were significantly increased (all P<0.05), and the expression levels of CHOP mRNA (0.92±0.36 vs. 0.38±0.08) and protein (2.79±0.79 vs. 1.06±0.23) of hippocampi tissue were significantly increased (both P<0.05) in PH group. Compared to PH group, the escape latency [(23.56±7.47) s, (13.62±6.36) s] and swimming distance [(2 234.64±890.58) mm, (1 120.67±389.74) mm] were significantly shortened (both P<0.05), W/D (2.92±0.64 vs. 5.47±0.98), TWC (1.86±0.84 vs. 4.43±0.97) and AI [(13.65±1.74)% vs. (36.32±2.62)%] were significantly reduced (all P<0.05), and the expression levels of CHOP mRNA (0.54±0.11 vs. 0.92±0.36) and protein (1.41±0.47 vs. 2.79±0.79) of hippocampi tissue were significantly reduced (both P<0.05) in UTI group. Conclusion The pretreatment of UTI could improve the long-term learning and memory function after PH in mice, which might be contributed to the inhibition of apoptosis mediated by CHOP in hippocampi tissue. Key words: Ulinastatin; CCAAT enhancer-binding proteins homologous protein; Partial hepatectomy; Cognition disorders; Postoperative complications