The mechanism of cytotoxic effects of hyperglycaemia on the brain has not yet been explained and the proposed hypotheses are not fully convincing. In the present study, we aimed to assess the effect of high doses of glucose on the ultrastructure of the mice brain. The results, which are in agreement with the literature data, show that the administration of a single high dose of glucose, as well as its chronic application, leads to accumulation of glycogen granules in the cytoplasm of astrocytes. A new observation is the detection of glycogen granules in the ultrastructurally changed mitochondria of astrocytes as well as in the mitochondria of some synapses. Our hypothesis assumes that excess of glucose may cause an increase in the vulnerability of the brain mitochondria. This in turn may enable glucose and cytoplasmic enzymes to penetrate into the mitochondria and they therein synthesise glycogen. Mitochondrial dysfunction may in turn lead to neurodegeneration by apoptotic process.