The molecular mechanisms involved in the regulation of synaptic plasticity in the hippocampus during the estrous cycle of the rat are not completely understood. Because this process implicates changes in neuronal cytoskeleton organization, we analyzed the content of microtubule associated protein 2 (MAP2) and Tau in the hippocampus and the frontal cortex of the rat by Western blot, as well as the hippocampal distribution of MAP2 during the estrous cycle by immunohistochemistry. In the hippocampus the lowest content of MAP2 was found on diestrus day, and it significantly increased at proestrus. This increase was maintained on estrus and metestrus days. In the frontal cortex MAP2 content did not significantly change during the estrous cycle. In contrast, the content of Tau did not vary during the estrous cycle in either the hippocampus or the frontal cortex. The immunohistochemical analysis showed an increase in dendrite thickness and in dendritic branching in the CA1 region on proestrus day, as well as an aggregation of MAP2 in apical dendrites near to pyramidal somata on this day in comparison with diestrus. We suggest that changes in the content and neuronal distribution of MAP2 are involved in the structural changes that occur in the hippocampus of the rat during the estrous cycle, and that these variations are related to changes in estradiol and progesterone levels.