Anti-diabetic activities of cultured mycelia from Ganoderma applanatum are being evaluated in this study. The OGTT and 4-weeks of repeated oral efficacy tests are conducted in mice at the doses of 0 (vehicle treatment), 25, 75 and 225 mg/kg/day, respectively. In human study, the test article was administered orally every day for 8-week at a dose of 1,500 mg/kg, tid and placebo group. The blood glucose levels (BGL) at 0.5 hour after treatment are significant decreased in all treatment groups of OGTT test. In the 4-week test, BGL of 75 and 225 mg/kg/day group is continuously decreased during all treatment periods and the BGL of 25 mg/kg/day group show decreasing trends at the final week, the pancreas weight of all treatment groups are being increased, and the Langerhans-islet numbers were increased at all treatment groups with a dose-response manner. There are no test article-related abnormal signs and the fasted blood glucose (FBG), postprandial blood glucose (PPG) and HbA1c are decreased significantly after 8-week treatments. These results that the cultured mycelia from Ganoderma applanatum could decrease BGL by protecting the degeneration of Langerhans islets.