Leptin receptor (LEPR) plays an important physiological role in energy metabolism. The study addressed the relationship between leptin receptor gene variations and type 2 diabetes mellitus (T2DM). Three single nucleotide polymorphisms (SNPs) of LEPR gene, Arg109Lys (A/G), Asn656Lys (C/G) and Pro1019Pro (C/T) were detected in a northern population in China. Totally, 317 patients with T2DM and 282 healthy controls were recruited randomly from urban communities in Harbin area in the Northeast of China. All polymorphisms were genotyped by Sequenom SNP detection system in both case and control groups. Linkage disequilibria analysis showed moderate linkage disequilibria between the pair-wise SNPs for all three SNPs. Then, we identified the haplotype covering the three SNPs (AGC) with higher risk of T2DM (OR=1.69 (1.09-2.61)), and showed that there existed significant difference between cases and controls (9.8% vs. 6.0%, P=0.02). We also observed significant difference in frequencies of the heterozygous haplotype combination (GGT/AGC), that is 17.0% vs. 8.2% in cases and controls, respectively (P=0.001). It further supported the evidence that the haplotype (AGC) was associated with T2DM. So, AGC haplotype in LEPR gene could be a risk factor associated with T2DM in Northern Chinese.