Silver nanoparticles (AgNPs) have been extensively applied to many industrial and biomedical fields due to their antibacterial effect. However, a large number of applications is also lead to health and environmental safety concerns. Up to date, it was well-known that AgNPs induced reactive oxygen species (ROS) production, cytotoxicity, pro-inflammatory effect, DNA damage, cell cycle disturb, necrosis and apoptosis by many researches. Also, several studies have been performed to investigate the microarray test for AgNPs in many cell types. However, no work reports the AgNPs toxicogenomic study in liver cell line and tissue until now. For this reason, we performed to in vivo toxicogenomic study for AgNPs inhalation exposed liver tissue. After 12 weeks inhalation exposure to AgNPs for the Sprague-Daley rats, we carried out silver concentration measurement for liver tissues and toxicogenomic analysis. As a result, we found that silver concentrations in livers were dose-dependently increased in male and female rats. However, a gender-different accumulation of silver in the livers did not observe. In toxicogenomic study, we observed that 109 and 150 genes significantly up-and down regulated by AgNPs inhalation exposure in male and female rats, respectively. The significantly altered male rat genes were involved in 54 biological pathways which were typically related with diabetes and metabolism. In female rat, the significantly expression changed genes were involved in 89 biological pathways which were mainly connected with metabolism and cell signaling. Plus, the gender-dependent gene expression changes of more than 2 fold were linked to 240 genes, with 114 genes in the male livers and 126 genes in the female livers. These were related to steroids and xenobiotics metabolism pathway.