We attempted to see whether or not gene expression of phosphatidylinositol 3-kinase (PI 3-kinase) is changeable in the hypoglossal nucleus of rats after hypoglossal nerve crushing by in situ hybridization histochemistry. After unilateral nerve crushing, an apparent enhancement of gene expression for PI 3-kinase was observed in individual neurons of the hypoglossal nucleus at the operated side on the first postoperative day, and it was sustained for 7 postoperative days. Thereafter the expression decreased at the operated side and no significant difference in the expression level was noticed between the operated nucleus and the contralateral, non-operated or sham-operated nucleus on postoperative day 14. The present study suggests that PI 3-kinase contributes to some important roles in morphological changes of mature neurons associated with nerve regeneration.