In this study, we investigated the regulation of Interleukin-18 (IL-18) and caspase-1 mRNA and protein levels in adipose and liver tissue of obese (ob/ob) mice compared with ob/+ mice. In ob/ob mice, which have a twofold higher IL-18 plasma level as compared with lean mice, IL-18 mRNA expression was significantly reduced by 1.6-fold in adipose tissue, whereas protein level was enhanced fourfold as compared with ob/+ mice. However, caspase-1 mRNA expression and activity were significantly enhanced in adipose tissue of ob/ob mice. Conversely, both IL-18 mRNA and protein levels were slightly enhanced, but caspase-1 activity was reduced in liver of ob/ob mice as compared with lean mice. In conclusion, we show that adipose and hepatic IL-18 protein expressions are increased in obese mice. However, in contrast to liver, the adipose IL-18 protein level appears to be upregulated through a post-transcriptional mechanism probably involving caspase-1.