The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism， serum leptin levels， soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52， CI = 1.18-5.35， p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49， p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8， CI = 1.6-85.1， p = 0.002] and an inverse association with cardiac disorder [OR = 0.09， CI = 0.02-0.46， p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4， p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus， it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.