A large number of studies have reported the action of K(ATP) channel openers in accelerating the proliferation of hepatocytes and many other cell types in vitro. Few studies, however, have examined the proliferative effect of K(ATP) channel openers in vivo. The aim of this study was to determine whether the K(ATP) channel opener minoxidil accelerates liver regeneration after partial hepatectomy (PH) in vivo. Male Wistar rats underwent a 70% partial hepatectomy (PH) after receiving a subcutaneous injection of minoxidil (0.01 mg/kg or 0.03 mg/kg). Some of the rats were intravenously treated with 5-hydroxydecanoic acid (5-HD, 10 mg/kg) just before the minoxidil injection. Seventy-two hours after PH, DNA synthesis was immunohistochemically assessed by bromodeoxyuridine (BrdU) incorporation into the nuclei. Minoxidil induced significant and dose-dependent increase in the BrdU labeling index after PH, and 5-HD reversed this minoxidil-induced change. Minoxidil did not significantly affect the changes in liver weight and liver function after PH. The hepatic levels of prealbumin decreased by about 60% after PH and minoxidil inhibited the decrease. In conclusion, the K(ATP) channel opener minoxidil enhanced DNA synthesis after PH without affecting the liver function.