The leptin system is implicated in the regulation of body weight and reproductive function, acting at endocrine and paracrine levels. This ligand-receptor system is mandatory for embryonic implantation in rodents. Here, we investigate the expression pattern of total leptin receptor (OB-R(T)), the long form (OB-R(L)) and short isoforms HuB219.1 and HuB219.3 in the human endometrium. Furthermore, we studied leptin and OB-R(T) mRNA during human embryonic preimplantation development and the embryonic regulation of the endometrial OB-R(L). Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part. Leptin receptor was localized at the epithelial and glandular epithelium using in situ hybridization. Reverse transcription-nested PCR showed the presence of OB-R(T) mRNA at all the embryonic stages, whereas leptin mRNA was only detected at the blastocyst stage. The embryonic regulation of endometrial epithelial OB-R(L) and HuB219.3 was studied, and no impact was found. Finally, OB-R(L) was immunohistochemically localized in the human cytotrophoblast and maternal decidua. These findings suggest that secretory endometrium is a target tissue for leptin action, and oocytes and preimplantation embryos possess OB-R mRNA, indicating that leptin may be necessary for embryonic development. Furthermore, leptin mRNA is specifically expressed at the blastocysts stage, suggesting a function in the blastocyst-endometrial dialogue.