Objective To explore method of rapidly establishing mild cognitive impairment models in rats by D-galactose (D-gal) and the appropriate dose. Methods Totally 100 male SD rats, the model groups A, B, C, D were given hypodermic injection of D-gal with the concentration of 100, 300, 1 000, 2 000 mg/(kg·day) respectively for 1 week, and the control group O received the same volume of saline. After injection, the Morris water maze (MWM) began, then the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and acetylcholinesterase (AChE) in the brain homogenate were determined, and the pathomorphologic changes of the hippocampus were observed by HE staining. Results (1) The survival rate of each group was 100%. The weight of group D gained less and the swimming speed was slower than in group O. (2) At day 2-5 of the place navigation test of MWM, the escape latencies in group C and D were prolonged as compared withthose in group O. For in the spatial probe test, the number of crossing the platform in 60 s of groups C and D was (3.05±0.76) and (2.05±0.69) respectively, significantly less than in group O (4.40±1.05, P=0.000, 0.000). (3) In groups C and D, the levels of MDA were (29.19±2.35) and (32.57±2.05) respectively, significantly higher than in group O [(20.52±2.08) ng/ml, P=0.000, 0.000]. The levels of SOD were (1.46±0.12) and (1.34±0.13) IU/ml respectively, significantly lower than in group O [(1.74±0.12) IU/ml, P=0.001, 0.000]. The levels of AChE were (3.52±0.70) and (4.02±0.39) ng/ml respectively, significantly higher than in group O [(1.72±0.33) ng/ml, P=0.000, 0.000]. (4) The pathomorphologic changes of the hippocampus showed: in group C, several pyramidal cells lost, density of cell was slightly decreased, pyknotic nucleis increased and some pyramidal cells were dark-stained and a small amount of apoptotic cells were seen in the CA1 region of hippocampus, while cerebral white matter was normal; in group D, density of pyramidal cells was significantly decreased, arrange was obviously loose and in a mess, and large number of cells were condensed, dark-stained and apoptosis occurred in the CA1 region. Conclusion Rats given hypodermic injection of D-gal with 1 000 mg/(kg·day) conformed to the pathological process and its characteristics of mild cognitive impairment. Key words: D-galactose; Mild cognitive impairment; Model, animal