Objective:To explore the establishment and assessment of the depression model of adult SD rats induced by early maternal infant separation stress combined with adult chronic unpredictable mild stress(CUMS), and to observe the behavior and synaptic protein expression of SD rats.Methods:Twenty-four male rats were randomly divided into three groups: control group (CON group), chronic unpredictable stress group (CUMS group), maternal infant separation combined with chronic unpredictable stress group (MS + CUMS group). The depression model of rats in cums group was established by CUMS, and the depression model of rats in MS + CUMS group was established by maternal infant separation + CUMS. The depression model was evaluated by body mass and appearance observation, sugar water preference experiment, open field test and forced swimming test.Synapse-associated proteins (PSD-95 and synaptophysin (Syn)) of the hippocampus were assayed using Western blot. Syn protein expression was measured by immunohistochemistry.Results:After modeling, compared with CON group, the rats in CUMS group and MS + CUMS group had significantly lower body mass((126.43±3.88) g, (91.04±3.85) g, (69.89±6.67) g; t=5.03, 8.03, both P<0.01), significantly lower sugar water preference((94.21±0.56)%, (79.30±1.13)%, (72.73±1.82)%; t=8.24, 11.87, both P<0.01) and significantly increased immobility time((3.50±0.84)s, (13.59±2.40)s, (15.70±2.97)s; t=3.16, 3.82, both P<0.01). Among them, the body mass and sugar water preference of MS + CUMS group were lower than those of CUMS group ( t=3.00, 3.63; both P<0.01). (2)The center time of the rats in MS+ CUMS group markedly reduced compared with that of CON group((21.41±4.65) s, (8.96±2.37) s; t=2.66, P<0.05). (3)In the immunohistochemistry experiment, compared with the CON group, the percentage of Syn positive area in hippocampus of rats in CUMS group and MS+ CUMS group decreased significantly ((24.42±0.76)%, (14.00±0.95)%, (10.38±1.38)%; t=6.93, 9.33, P<0.01). (4)The results of Western blot showed that compared with CON group, both the expression of PSD-95 ((1.18±0.02), (0.74±0.06), (0.52±0.05), t=6.29, 9.31; both P<0.05) and Syn ((1.12±0.08), (0.95±0.06), (0.90±0.07); t=3.10, 4.04; both P<0.05) in hippocampus of rats in CUMS group and MS+ CUMS group were significantly decreased.And compared with the CUMS group, the expression of PSD-95 in MS+ CUMS group was lower( t=0.93, P<0.05). Conclusion:The method of MS combined with CUMS can effectively induce depression like behavior and decrease the expression of synaptic plasticity related protein of hippocampus in rats.