Objective: To investigate the influence of sodium selenite on adiponectin expression in kidney of rats with diabetic nephropathy and the relation between sodium selenite and adiponectin, so as to investigate the role of sodium selenite and adiponectin in diabetic nephropathy. Methods: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and high fat diet. The study was divided into 3 groups, namely, a control group, a diabetic nephropathy group and a selenite-treated group. Animals in the selenite-treated group were given selenite solution 1 μg/kg daily via intragastric administration; those in the other 2 groups were given the same dose of saline in the same way. The animals were sacrificed 10 weeks later and the blood and urine samples were used for biochemical examination. Samples of renal cortex were cut quickly and fixed with 4% glutaral for observation under scanning electron microscope. The renal samples were made into paraffin section for observation of the pathological changes under light microscope and for location of protein expression via immunohistochemistry analysis. The expression of adiponectin mRNA and protein was examined by real-time PCR and Western blotting, respectively. Results: The general condition and biochemical parameters of animals in the selenite-treated group were obviously improved and the pathological changes were obviously releived compared with those in the diabetic nephropathy group. Immunohistochemistry analysis showed that the expression of adiponection in the selenite-treated group was obviously stronger than that in the diabetic nephropathy group, and the expression was found in both glomerulus and renal tubule. The expression of adiponectin mRNA in the selenite-treated group and diabetic nephropathy group was 2.043 and 1.373 folds that of the control group, respectively. The expression of adiponectin protein in the selenite-treated group was significantly higher than those in the control group and diabetic nephropathy group (P<0.05). Conclusion: Sodium selenite can enhance renal expression of adiponectin through antioxidative stress and promotion of periphery tissue sensitivity to insulin, indicating that sodium selenite and adiponectin may play important roles in delaying the progression of diabetic nephropathy.