Maternal high-fat diet (HFD) during pregnancy and lactation induces depression-like phenotype and provokes myelin-related changes in rat offspring, which persist even to adulthood. Due to the plasticity of the developing brain, we decided to analyze whether depression-like phenotypes and myelin-related changes in the early lifetime induced by maternal HFD could be reversed by the omega-3 fatty acid-enriched diet (Ω3D). We investigated the effects of the Ω3D from the post-weaning period until adulthood (63rd day of life) in offspring on the depressive-like behavior (forced swimming test, locomotor activity) induced by the maternal HFD (60% energy from fat) during gestation and lactation. Next, we analyze the effect of post-weaning Ω3D on the myelin-related changes (RT-qPCR, Elisa, immunofluorescence staining) in the prefrontal cortex (PFCTX) of adult offspring. Ω3D reversed increased immobility time in adult offspring induced by maternal HFD, without affecting the animals' locomotor activity. Molecularly, Ω3D normalized the reduced expression levels of myelin-oligodendrocyte glycoprotein (MOG) and myelin and lymphocyte protein (MAL) in males and MOG in females in the PFCTX, changes initially induced by maternal HFD. Additionally, Ω3D normalized the number of oligodendrocytes (precursor and mature cells) in the prelimbic, infralimbic, and cingulate cortex mainly in males, which were reduced following maternal HFD exposure. These findings suggest that Ω3D may play a significant role in correcting behavioral and neurobiological changes caused by adverse prenatal conditions.This study was supported by the research grant UMO-2020/39/D/NZ5/02581 (SONATA 16) from the National Science Center, Kraków, Poland.