This study aims to investigate the changes of microtubule-associated protein 2 (MAP-2) in epileptic dentate gyrus and significance in epilepsy. Alterations in MAP-2 immunoreactivity (MAP2-IR) in kindling model of epilepsy were investigated in rats with survival times ranging from 3 to 30 days. Nissl staining and electron microscopic studies were used to explore more deeply. Electron microscopic was employed to detect tubulin formation and assembly. Immunohistochemical assay was used to examine co-localization of tubulin and MMP-2. Results indicated that MAP2-IR obviously enhanced in dendrites of granule cells 3 days after kindling and remained enhanced up to 14 days (P < 0.01). It returned to control patterns 20 to 30 days after kindling (P < 0.01). Nissl staining demonstrated a negative correlation between enhancement of MAP-2 and degeneration of hilar neurons (r = -0.9274). Electron microscopic studies showed that microtubules of dendrite in dentate molecular increased 3 days after kindling and obviously increased 14 days after kindling (P < 0.05). Tubulin protein showed a well co-localization with MMP-2 protein. Treatment of paclitaxel significantly decreased tubulin formation and assembly compared with untreated group (P < 0.01). Sprouting of dentate granule cell axons and synaptic contacts between nerve terminal and dendrite were discovered. Overexpression of MAP-2 via formation of microtubules plays an important role in the sprouting of mossy fibers in epileptic rats.