Summary 　Adiponectin, a physiologically active polypeptide secreted by adipocytes which exists abundantly in serum, shows insulin-sensitizing, anti-inflammatory and anti-atherogenic properties in rodents and humans. To find out the new effects of adiponectin in vivo, the model animal with hyperadiponectinemia has been needed. We fortunately succeeded to produce three lines of transgenic mice expressing human adiponectin in the liver. Two lines of these mice of had serum human adiponectin levels 20 times higher than normal human and exhibited 30 times higher serum levels of high molecular weight (HMW). We reported that these mice with hyperadiponectinemia had long life-span. Especially, the longevity effect of adiponectin under a high calorie chow was more remarkable than under a regular chow. Calorie restriction has only been established as a way of longevity in all species. If the fact that detailed functions of adiponectin lead to longevity will be identified, the development of calorie restriction mimetic or exercise mimetic might become possible.