Objective To obtain more physiological data of Leptin knockout SD rats available for the user, the long-term observation of fasting blood glucose and pathological phenotypes were performed. Methods The protein expression levels in liver tissues were determined by western blot. Body weight of Leptin knockout rats (Leptin-/-) and littermate lean rats (Leptin+/+) were weighed up at 1,3,6,8 months of age. Fasting blood glucose of Leptin+/+ rats and Leptin-/- rats at 1,3,6,8 months of age were measured using One Touch brand blood glucose monitoring systems. Pathological changes of pancreas and livers of Leptin-/- rats were observed by the method of HE staining and Immunohistochemistry (IHC). Results Short null Lepin proteins were expressed in liver tissues from Leptin-/- rats. Leptin-/- rats become heavier than Leptin+/+ rats since they were one month old. The body weight of Leptin-/- rats at 8 months of age was twice as heavy as Leptin+/+ rats, female Leptin-/- rats weighing 884g, and male Leptin-/- rats weighing 1200g. Overt hyperglycemia was observed during the first month after birth. Compared with Leptin+/+ female rats,the fasting blood glucose of Leptin-/- female rats was increased by 40%-26% from 1 to 6 months old. After that, blood glucose values decreased and eventually become nearly normal at 8 months of age. Pathological examination indicated that Leptin-/- rats at 8 months of age had a fatty liver, more pancreas islets with lager volume and more beta cells with increased insulin secretion. Conclusion Leptin-/- rat were characterized by obesity, fatty liver, islet cell hyperplasia and early hyperglycemia.