Objective To study the expression of lipoic acid synthase (LIAS) in the liver and kidney of Lepr ^db/db mice with deficient leptin receptor. Methods Eight 10?week old male Lepr ^db/+ mice and Lepr ^db/db mice were included in this study. The body weight of rats in the two groups was measured. Fasting blood glucose (FPG) was measured with blood glucose test strips for all mice after fasting for 8 hours. Blood samples were obtained from the abdominal aorta and the animals were sacrificed. The liver and kidney were weighed. The right lobe of liver and the left kidney samples were fixed in 4% paraformaldehyde for pathological examination. Serum samples were separated and the sereum contents of CHO, TG, HDL and LDL were detected. The mitochondria of liver and kidney tissues were extracted with a mitochondrial isolation kit, and the protein was extracted. The expression of LIAS protein was detected by western blot. Results Histopathological observation showed that the liver and kidney tissues of Lepr ^db/+ mice have intact and clear structure. But the liver tissue of Lepr ^db/db mice showed fatty degeneration, the kidney tissue showed glomerular hypertrophy, basement membrane thickening, mesangial area widened, including mesangial cells and mesangial matrix increased. The GLU, CHO, TG, LDL and AST of Lepr ^db/db mice were significantly increased compared with those of Lepr ^db/+ mice ( P < 0.05). Compared with Lepr ^db/+ mice, the LIAS protein expression was significantly increased in the liver and kidney mitochondria of Lepr ^db/db mice ( P <0.05). Conclusions There is impaired glucose and lipid metabolism in the Lepr ^db/db mice which has defect leptin receptor, and the expression of LIAS protein in liver and kidney of the Lepr ^db/db mice is higher than that of Lepr ^db/+ mice.