Neural plasticity was considered as the principal mechanism for learning and memory many decades ago. So our study aims to figure out the underlying mechanisms of myelin plasticity associated with learning and memory. Myelin was considered for a long time as static, inert insulator, irrelevant to learning. But recent studies showed that myelination is dynamically changed to enhance neuronal plasticity. The study was conducted on 24 rats, divided into 3 groups, with 8 rats in each: Group 1: control in cages; Group 2: control untrained; and Group 3: rats were trained using Barnez maze behavior test. The gene expression analysis for Sox10, Myrf, Nrg1, Bdnf, Serpine2 and Mbp was evaluated by qRT-PCR in hippocampus tissues with correlation assessment, and histopathological and immunohistochemistry assessment were done. The present study showed improved spatial memory with increased myelination in the trained group, in addition to high expression of Sox10, Myrf, Nrg1 and Bdnf in the trained group compared to all others (P < 0.001). Serpine2 and GFAP as markers of astrocytes showed high expression in the trained group in comparison with other groups (P < 0.001) with strong positive correlation between Serpine2 and Mbp (r = 0.76, P = 0.02). Myelin plasticity as one of the crucial learning mechanisms, was influenced by different neural and environmental signals. In addition, there was a significant role of astrocytes in promoting such myelination effect.