PURPOSE:Background: Bevacizumab is one of the anti vascular endothelial growth factor (anti-VEGF) agents which has antiangiogenic and oedema-diminishing actions. It is used widely as an intravitreal solution to diminish new vessels formation and reduce the oedema of the ocular diseases. Objectives: to evaluate the safety of an intravitreal injection of bevacizumab on the cerebral cortex of rat. Material and methods: 20 animals were used in the experiment. They were divided into two groups 10 animals each. Group I: rats were injected with saline as a 5 uL single injection into the vitreous cavity of the left eyes. GroupII: rats were injected with 5 uL (25 mg/mL) of bevacizumab as a single injection into the vitreous cavity of the left eyes. Animals were sacrificed 4 days after injection. Brain was dissected and processed for light and electron microscopy. Results: Microscopic examination revealed various histological changes in the nerve cells. Some of them had pyknotic nuclei and acidophilic cytoplasm. This was associated with astrocyte gliosis as well as widening of both pericellular and perivascular spaces. Vacuolations of the neuropil was also observed. Others had irregular nuclei, numerous cytoplasmic vacuoles and dilated rough endoplasmic reticulum. Apparent decrease of free ribosomes was also observed. There was highly significant increase in the number of glial fibrillary acidic protein immunostained positive cells (astrocyte gliosis). Conclusion: intravitreal injection of bevacizumab had toxic effect on the cerebral cortex of rat..