Background: Genetic variations in the engulfment and cell motility 1 (ELMO1) gene have recently been identified to be associated with nephropathy attributed to Type 2 diabetes mellitus (T2DM). Since T2DM-associated complications are proved to be more common among Asians than Western individuals, and Chinese people have a high incidence of diabetic nephropathy (DN), this study sought to analyze the association of ELMO1 gene polymorphisms with DN to probe into the effects of ELMO1 gene on susceptibility of DN in Chinese population. Methods: We genotyped 6 polymorphism sites of ELMO1 gene in 200 unrelated Chinese subjects (123 T2DM with DN case subjects and 77 T2DM without DN control subjects). Genotyping was detected by a Sequenom MassARRAY genotyping system. Results: The strongest associations in ELMO1 gene with DN occurred at rs741301 [odds ratio (OR) 1.89; p=0.004] and rs10951509 (OR 1.76; p=0.02). Unconditional logistic regression analysis identified that the rs741301 polymorphism (presence of A allele, adjusted OR 3.27; p=0.03) and duration of T2DM (adjusted OR 1.15; p=0.04) were independent predictors for DN. The marker rs741301 located in intron 18 of ELMO1 gene was in strong linkage disequilibrium (LD) with rs11769038 (D′=0.91). Furthermore, haplotype analysis identified that haplotype 1 [CAAAGA] (OR 1.95; p=0.01), haplotype 2 [CAAAGG] (OR 0.50; p=0.01), and haplotype 9 [TGCGGG] (OR 0.17; p=0.007) of ELMO1 were significantly associated with DN. Conclusions: This study first investigated the association of ELMO1 gene polymorphisms with DN in a Chinese population, supporting its key role as a candidate gene in the susceptibility of DN.