Leptin and adiponectin are the most abundant adipokines that regulate energy homeostasis. Here, we report the changes of leptin and adiponectin in response to age and their depot-specific expression in lean and genetically obese mice. Fat deposition patterns, adipokine levels and their adipose-tissue depot-specific expression patterns were examined in both sexes of lean and obese mice on two different diets at four and 20 weeks. In obese mice, body fat mass was higher than in lean mice and was increased with age. Leptin levels correlated with body fat mass and therefore increased with age. Leptin levels were correlated higher with the weight of subcutaneous than with the weight of reproductive adipose tissue. Likewise, leptin mRNA levels in subcutaneous adipose tissue corresponded well with serum leptin levels. Adiponectin levels did not differ significantly between the ages and did not correlate with body fat mass or with either of the adipose-tissue depots, although obese mice had lower adiponectin levels than lean mice. Nevertheless, serum adiponectin levels showed a pattern of changes that was similar to that of the adiponectin transcript amounts in the reproductive adipose tissue. Our results confirm that serum leptin levels are regulated by the body fat mass, predominantly by the subcutaneous adipose tissue mass. Furthermore, our data provide evidence that serum adiponectin levels are influenced by other factors than body fat mass alone.