The aim of this study was to investigate the relationship between the leptin receptor (LEPR) polymorphism/serum leptin level and preeclampsia. The prevalence of a single nucleotide polymorphism in the LEPR gene exon 14 at -656 and the serum leptin concentrations in 97 preeclamptic pregnant mothers were compared to those of 110 healthy controls. The Lys656Asn genotype and Lys656Asn + Asn656Asn frequencies in the LEPR gene were significantly more prevalent in preeclampsia mothers than in controls (P < 0.05). The serum leptin levels of preeclampsia cases were significantly higher than those of controls. In addition, there were higher serum leptin levels in individuals with the GC + CC genotype both in the total cohort and in women with preeclampsia than in those with the GG genotype. Our findings suggest that the Lys656Asn polymorphism is a functional variant in the LEPR, which can affect the interaction of leptin and its receptor. Furthermore, high leptin level and the LEPR variant are risk factors for preeclampsia in Chinese women.