Continuous maturation of cerebral white matter (WM) in the postadolescent period is not fully understood. To elucidate the time course and location of possible postadolescent maturational changes in cerebral WM, we studied 60 healthy male subjects who were in their second to seventh decade using diffusion-weighted imaging. Mean diffusivity (MD) in subcortical WM was measured in 78 cortical regions in each subject's brain using an automated method. Regression analysis was used to model the age-related change in MD by either a linear or a quadratic function in each region. Age-related changes in subcortical MD were best modeled by either a linear function or a quadratic function in 27 regions including language-related regions, visual or multimodal areas in the bilateral occipital and temporal lobes, limbic areas including the bilateral parahippocampal gyri, and the bilateral postcentral and left precentral gyri. In these regions, the MD rapidly decreased until middle age and thereafter reached a plateau. Our results revealed microstructural changes in local subcortical WM and suggests a continuing maturational process in postoadolescent periods.