This study was conducted to demonstrate the possible protective and therapeutic effects of naringenin, an estrogenically effective flavonoid, in experimental autoimmune encephalomyelitis (EAE) which is the rodent model of multiple sclerosis. For this purpose, fifty, 12-week-old C57BL6 male mice were divided into five groups; Control, naringenin, EAE, prophylaxis and treatment. EAE model was induced with myelin oligodendrocyte glycoprotein (35-55) , and naringenin (50 mg/kg) was administered by oral gavage in the prophylaxis, treatment and naringenin groups. Naringenin’s preventive and therapeutic effects were examined according to clinical, histopathological, immunohistochemical and RT-PCR (aromatase, 3βHSD, estrogen receptors and progesterone receptor expressions) parameters. Aromatase immunopositivity rates decreased while 3βHSD, estrogen receptor α&β and progesterone receptor immunopositivity rates increased in mice with EAE. On the other hand, RT-PCR results showed that aromatase, 3βHSD, estrogen receptor-β and progesterone receptor gene expressions were decreased, while estrogen receptor-α increased after EAE induction. Naringenin improved aromatase immunopositivity rates and expressions in both prophylaxis and treatment groups. Clinical and histopathological findings revealed that EAE findings were alleviated in both prophylaxis and treatment groups along with significantly decreased inflammatory cell infiltrations in the white matters of the spinal cords. In conclusion, naringenin could provide long-term protection by creating effects similar to estrogenic stimulation due to stimulating the expression of aromatase, even in prophylactic use. It’s also postulated that the better results obtained in the treatment group were due to naringenin’s anti-inflammatory effects at a certain concentration in the plasma or tissue.