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Visual impairment is considered as the most common initial manifestation of multiple sclerosis (MS) patients. It has been shown that hesperetin (Hst), a flavonoid of citrus fruit, possesses anti-inflammatory and antioxidant effects both in vitro and in vivo. The present study was designed to evaluate the pharmacological/medicinal effects of Hst treatment on myelin repair and glial activation in lysolecithin (LPC)-induced focal demyelination model. In order to induce local demyelination model, LPC 1% (2μL) was injected into the optic chiasm of rats. Animals received oral administration of Hst at dose of 20mg/kg for 14 or 21days post lesion induction. Visual evoked potential (VEP) recordings were conducted before and also on days 7, 14 and 21 post LPC injection. Glial activation and myelination of optic chiasm were evaluated by immunostaining on brain sections. Analysis of VEPs data revealed that oral administration of Hst effectively reduced the latency of N1 waves. Immunostaining results showed the reduced number of astrocytes and microglia in animal which were treated with Hst. Furthermore, the extent of demyelination area was decreased in animals treated by Hst. Taken together; our results suggest that Hst treatment significantly protects and repairs myelin sheath, therefore it might be regarded as effective supplementary agent in demyelinating disorders, particularly MS.