In this article we report the healing effects of a Phellinus linteus fruiting body hot water extract (PLE) in streptozotocin (STZ)-induced diabetic rats. PLE was given before and after STZ. The preprotective, protective, and postprotective effects of PLE on STZ-induced oxidative stress were studied using biochemical (caspase 3 activity, cytosolic-to-lysosomal ratio of cathepsin B and L, DNA fragmentation levels), ordinary histological and immuno-histochemical investigation parameters. Following oral administration of PLE after STZ application, the serum glucose concentration significantly decreased up to 41.13% compared with the control group (P < 0.05). The hypoglycemic potential of the PLE was further supported by an increase of insulin secretion in the islets of Langerhans. In addition, the number of cells in Langerhans islets increased by 45.89% when PLE was given after STZ application. On the other hand, the use of PLE before oxidative stress could not prevent the onset of diabetes. This is, to our knowledge, the first study of the effect of application time of orally administered Ph. Linteus hot water extract on STZ-induced diabetes.