Objective To investigate the effects of lentinan (LNT) on lipid peroxidation and NO level in brain tissues of diabetic rats. Methods\ Twenty nine male Sprague Dawley rats were randomly divided into three groups: normal control group(n=10), diabetic group(n=10) and LNT treatment group(n=9). The morphological changes of brain tissues were examined by light and electron microscopy. The activity of superoxide dismutase(SOD), nitric oxide synthase(NOS) and content of malondialdehyde (MDA), nitric oxide (NO) in the brain tissues were assayed by spectophotometer, respectivly. Results Cerebral edema, encephalomalacia,demyelination in the white matter were observed by histopathology. Swelling and criste loss of mitochondria in neurons and neuroglial cells, demyelination of nerve fibers and vascular endothelial cell damages were seen by electron microscopy. The activities of SOD in diabetic brain tissues was decreased; but the activities of NOS and content of NO increased in comparison with those of control group. After treatment with LNT, the activities of SOD were increased and NOS activity, content of NO and MDA were decreased in comparison with those in diabetic rats. Conclusion LNT possesses effects on prevention of brain tissue damages in diabetic rats by enhancement of anti oxidation activities and reduction of NO level.