Mortality of obese patients with sepsis has been reported to be significantly higher than lean patients. The underlying basis for this difference is not currently known. However, it has been suggested that obesity is associated with an altered immune response to a septic or inflammatory insult. Since obesity is based on exclusion in many sepsis trials, little is known about how obesity affects mortality or whether obese individuals respond differently to therapeutic interventions. In this study, obese and non-obese mice were given intra-peritoneal injection of saline or LPS and the livers were harvested 2 hours later. RNA from these livers were subjected to DNA microarray. Analysis showed distinct differences in gene expression between lean and obese animals. The expression of one hundred and seventeen genes was found to be different among the groups. In the obese animals treated with LPS, the expression of 20 genes showed a significant change. Ontology analysis revealed increased expression of 15 genes and significant decrease in expression of 5 genes. This study shows different gene expression of liver in response to LPS in lean versus obese animals. These genes might play a role in the outcome of sepsis.