Objective To observe the effect of propofol on cognitive functions and hippocampus tissue in hyperlipidemia aged rats.Methods Seventy-six aged male SD rats were selected and randomly divided into basal diet with propofol injection (group PI), basal diet with normal saline injection(group N1), high-fat diet with propofol injection (group P2) and high-fat diet with normal saline injection (group P2), with 19 rats in each group.Eight weeks later,group P1 and P2 received intraperitoneal injection of propofol 100 mg · kg-1 · d-1 for 5 days.While in group N1 and N2, rats received the same intraperitoneal injection of equal volume normal saline.One day after the last injection, escape latency and space exploration were detected by Morris water maze in the next six days.One hour after the last water maze test, the serum and hippocampus were sampled to detect the expression of beta-amyloid protein and receptor for advanced glycation endproducts(RAGE) by immunohistochemical method and ELISA respectively.Results In place navigation tests,the escape incubation period(98.20±25.40)s in group P1 was obviously longer than that in N 1 group (47.50± 11.08) s (P＜ 0.01).Compared with P2 (99.79 ± 20.38) s, escape incubation period was shortened in N2 (50.70± 20.55) s (P＜ 0.05).There was no significantly difference between N2 and N1 (P＞0.05), while the escape incubation period in group P2 was longer than P1 (P＜ 0.05).In spatial probe test,platform passing number ((2.86 ±1.46)times) in group P1 were less than that in N1 group ((7.50± 1.70) times, P＜0.05).In group N2, the platform passing number ((6.60 ±3.91) times) were more than those in group P2 ((1.16 ±1.16)times, P＜0.05) while there was no significant difference between group N1 and N2 (P＞0.05).Times of crossing platform in group P2 were less than that in P1 group (P＜0.05).Compared with group N1((147.83±60.88) ng/L) and N2((152.73±87.50) ng/L) ,the expression of RAGE protein was increased in group P1((629.89±110.33) ng/L) and P2((229.89±53.20) ng/L) (P＜0.05).There was no significant difference between N1 and N2 groups(P＞0.05) ,while the expression of RAGE protein in P1 group was lower than that of P2(P＜0.05).In immunohistochemical test, positive expression cells in P1 ((18.49± 1.53) and P2 (25.67±3.08)) were higher than that in group N1(9.33±2.31) and group N2(12.14±2.52) (P＜0.05) ,while there was no significant difference between group N1 and N2(P＞0.05).Conclusions Anesthetic dose of propofol can injure spatial learning and memory ability in aged rats.Hyperlipidemia might act synergistically with propofol.