OBJECTIVE To verify the effects of octreotide on liver gluconeogenesis in high fat diet-induced obesity rat. METHODS Male SD rats were randomly assigned to control (n = 16) and high-fat diet group (n = 40). After 24 weeks, obese rats selected from high-fat diet group were placed into obese group (n = 16) and octretide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h (40 mg/kg body weight) for 8 days. Body lengths, body weight, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), fasting serum insulin and plasma somatostatin (SST) levels were measured. The Lee' s index and HOMA index were calculated. Expression of glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (Pepck) and forkhead box-containing protein 0 subfamily-1 (Foxol) mRNA were measured by RT-PCR. Foxol protein in nuclear and cytoplasm were quantified by western blotting. RESULTS Compared with control group, body weight, FPG, TG, TC, insulin and HOMA index in obese group were significantly increased. Octreotide treatment showed obviously reduced levels of the parameters. The plasma SST levels in the obese group tended to decrease compared with that in the control group (P >0. 05), while plasma SST levels was increased in the octreotide-treated group compared with that in the obese group (P <0. 05). Obese rats display more G6pase, Pepck and Foxol mRNA and higher ratio of nuclear Foxol protein to cytoplasm Foxol protein than control rats (P < 0. 01), whereas octreotide intervention reversed those changes (P <0. 01). CONCLUSIONS The administration of octreotide can ameliorate abnormal enhancement of hepatic gluconeogenesis, which might be attributed to the reduced activity and expression of Foxol and then decreased expression levels of G6pase and Pepck mRNA.