Objective To investigate the relationship between leptin gene promoter G-2548A (rs7799039) polymorphism and type 2 diabetic nephropathy. Methods A total of 416 Patients with type 2 diabetes were selected, who were in hospital in the affiliated hospital of North China University of Science and Technology from May 2016 to May 2017. There were 224 cases in no diabetic nephropathy group with 102 males and 122 females, and the average age was (56.2±11.1). The other 192 cases were in type 2 diabetic nephropathy group with 96 females and 96 females, and the average age was (58.3±11.5). The study adopted the method of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes of G-2548A and comparison of differences between genotypes and allelic polymorphisms. Results ① There were statistical significance of the differences in serum leptin levels, urea nitrogen, creatinine, glycosylated hemoglobin, systolic blood pressure and diastolic blood pressure among no diabetic nephropathy group and type 2 diabetic nephropathy group (P < 0.05), while there was no statistical significance of the differences in related index of uric acid and blood lipids (P > 0.05).②The genotype distribution and allele frequency of G-2548A in diabetic nephropathy group and type 2 diabetic nephropathy group were statistically significant (P < 0.05). Conclusions The distribution of G-2548A genotype in leptin gene promoter region and allele polymorphism have some correlation with type 2 diabetic nephropathy. The A allele may be a susceptible gene for the development of type 2 diabetic nephropathy.