The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2 g l(-1) for 14 days. As expected, treatment with cilnidipine decreased the systolic and diastolic blood pressures in DIO mice, compared with control mice (P<0.05 for each parameter). Cilnidipine treatment improved glucose and insulin sensitivity in DIO mice. In addition, cilnidipine treatment dramatically increased the level of adiponectin in white adipose tissue (P<0.05) and the circulating levels of total and high-molecular weight (HMW) adiponectin in DIO mice (P<0.01 for each parameter). Furthermore, the secretion of HMW adiponectin and the ratio of HMW adiponectin/total adiponectin were both increased after cilnidipine treatment. Finally, the secretion of adiponectin from adipocytes was increased after cilnidipine treatment. Taken together, these results indicate that cilnidipine improves insulin tolerance and adiponectin levels, especially high-molecular type adiponectin, in DIO mice.