Sinusoidal endothelial liver cells (SECs) have a key role in the pathophysiology of chronic liver disease. Leptin is an important profibrogenic and proinflammatory cytokine whose expression in sinusoidal endothelial liver has not been documented. The authors studied the potential of rat SECs to express the leptin and leptin receptor genes. Two cell lines of rat SECs were generated from a male rat liver by pronase-collagenase perfusion and dilution cloning. They were characterized according to morphology, ploidy, von Willebrand antigen immunoreactivity, CD31 transcription, matrix metalloproteinase secretion, and pseudocapillary formation. Expression of the leptin and leptin receptor genes was studied using qualitative reverse transcriptase-polymerase chain reaction. Both cell lines fulfilled the accepted criteria for consideration as being derived from the liver sinusoidal endothelium. Confluent monolayers of both cell lines transcribed leptin and leptin receptor genes. This work demonstrated that SECs can transcribe the leptin gene in vitro, cotranscribing with the leptin receptor gene. Leptin production and signaling at this level could be of paramount importance in liver physiopathology; further studies of this issue are warranted because it represents a potential intervention point during chronic liver diseases.