Chronic unpredictability mild stress (CUMS)model was used to investigate the effects of different dietary patterns on anxiety and depression-like behaviors in mice. C57BL/6 mice were randomly divided into normal diet group (ND), normal diet stress group (NDS), high fat diet group (HFD) and high fat diet stress group (HFDS). The behaviors, body weight, lipid profiles and neurotransmitters were measured. The results showed that compared with the ND group, the sucrose preference of HFD group was significantly decreased, and the total movement distance, the number of entering the central area and the number of crossing squares were decreased in the open field test. Some behavioral indexes of HFDS group were lower than those of HFD group, and some behavioral indexes in HFDS group were lower than those in NDS group. The body weight, adipose/weight, TC, and TG levels of HFD group were higher than other groups, and CUMS significantly reduced the adipose/weight, TC, and TG levels in mice fed high-fat diet and normal diet, and these lipid indexes were lower in HFDS group compared with NDS group. The contents of 5-HT and NE in HFD group were lower than those in ND group. CUMS significantly decreased the levels of 5-HT and NE in serum and hippocampus of high-fat diet and normal diet mice, and the levels of neurotransmitters in HFDS group were lower than that in NDS group. The results suggested that high-fat diet can easily induce anxiety and depression-like behaviors, and high-fat diet could also aggravate CUMS-induced anxiety and depression behavior, which may be related to lipid metabolism and central neurotransmitter metabolism pathways.