Objective To explore the effect of a long-term high protein diet on liver and adipose tissues of ovariectomy (OVX) mice and the role of glucagon-like peptide-1 (GLP-1). Methods 32 8-week-old C57BL/ 6 female mice were randomly divided into control (Control), model (OVX), high protein (OVX+HP) and low protein (OVX+LP) groups with eight rats in each group. After ovariectomied, OVX, OVX + HP and OVX + LP groups were provided with standard, high protein and low protein diets, respectively. The control group received the same operation to preserve the ovaries and were provided with a standard diet. The mice were weighed weekly and sacrificed at the end of 24^th week. The liver, colon and retroperitoneal adipose tissue were collected, and retroperitoneal adipose tissue was weighed. HE staining was used to observe pathological changes of the liver and retroperitoneal adipose tissue. An enzyme-linked immunosorbent assay was used to measure serum GLP-1 levels. Real-time quantitative PCR was used to measure the expression of sterol regulatory element-binding protein-1c (SREBP-1c) in the liver and GLP-1 in colon tissues. Immunohistochemical staining was used to detect expression of SREBP-1c protein in the liver. Results At the end of 24^th week, compared with the control group, the OVX group gained weight (P<0. 05) and retroperitoneal adipose tissue was increased (P<0. 05). A large number of lipid droplets in hepatocytes and the retroperitoneal adipocyte volume were increased in the OVX group. GLP-1 mRNA expression in colon tissues of the OVX group was decreased (P<0. 05), and the serum GLP-1 content in the OVX group was also decreased (P<0. 05). SREBP-1c mRNA and protein expression in liver tissues was increased in the OVX group (P<0. 05). Compared with the OVX group, the OVX+HP group showed a decrease in body weight (P<0. 01) and a significant decrease in retroperitoneal adipose tissue (P<0. 001). A small amount of lipid droplets was observed in hepatocytes, and retroperitoneal adipose cells had shrunk in pathological sections of the OVX+HP group. GLP-1 mRNA expression in colon tissues was increased in the OVX + HP group ( P< 0.01). Serum GLP-1 content was significantly increased in the OVX+HP group (P<0. 001). SREBP-1c mRNA and protein expression in liver was decreased in the OVX +HP group ( P < 0. 001). There was no statistically significant difference in weight, retroperitoneal fat and the mRNA expression of GLP-1 and SREBP-1c between OVX+ LP and OVX groups. Conclusions A long-term high protein diet improved weight gain and liver steatosis in OVX mice, which may be related to the high protein diet promoting GLP-1 secretion in intestines and downregulating the protein expression of SREBP-1c in the liver, which plays a similar role to estrogen.