【Abstract】Objective Leptin is a cytokine that is involved in the regulation of energy intake and expenditure, neurogenesis, immunity and lipid and glucose metabolism. Because the characteristics of metabolism and physiology in rats are more close to those of human beings than those of mice, Leptin-/- rat provided a good model to assess those effects. Methods Transcription activator-like effector nucleases (TALENs) was used to disrupt the rat Leptin locus, creating heritable mutations that eliminate leptin function. The body weight of Leptin-/- rat was recorded at 4-16 weeks of age. The subcutaneous and visceral adipose tissue was measured by MRI and the histopathology of pancreas was observated under light microscope. Serum biochemicals, intraperitoneal glucose tolerance test (IPGTT) and glucose stimulated insulin secretion were determined at 4-months-old Leptin-/- rat. Results A F0 rat with the 8-bp deletion in Leptin gene ranging from 418 to 425 base pairs was gained, C-terminal 28 amino acids of Leptin were deleted. The body weight of Leptin-/- rat increased significantly from 5 weeks of age, and at 4-months-old increased by 52% compared with that of Leptin+/+ rat. Increased body weight mainly caused by excessive accumulation of subcutaneous and visceral adipose tissue by MRI, Histopathology observation showed that total islet volume of Leptin-/- rat was higher than Leptin+/+ rat at 2-months of age. Triglyceride and cholesterol levels in Leptin-/- rats were 8.4 and 1.8 times as high as those of Leptin+/+ rats at 4 months of age. Hyperinsulinemia and glucose intolerance was observed in Leptin-/- rats at the same age. Conclusion The Leptin-/- rats were created using TALENs. Our initial characterization showed that the Leptin-/- rats were obese, hyperinsulinemia, hyperlipoidemia and glucose intolerance. The Leptin-/- rats could be used as the model for lipid and glucose metabolism, neurogenesis and immunity.