IntroductionMany studies have reported brain volume changes in smokers. However, the volume differences of grey matter (GM) and white matter (WM) in young and middle-aged male smokers with different lifetime tobacco consumption (pack-years) remain uncertain. ObjectivesTo examine the brain volume change, especially whether more pack-years smoking would be associated with smaller gray matter and white matter volume in young and middle-aged male smokers. MethodsWe used a 3T MR scanner and performed Diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry on 53 long-term male smokers (30.724.19 years) and 53 male healthy non-smokers (30.835.18 years). We separated smokers to light and heavy smokers by pack-years and compared brain volume between different smoker groups and non-smokers. And then we did analysis of covariance (ANCOVA) between smokers and non-smokers by setting pack-years as covariates. ResultsLight and heavy smokers all displayed smaller GM and WM volume than non-smokers and more obviously in heavy smokers. The main smaller areas in light and heavy smokers were superior temporal gyrus, insula, middle occipital gyrus, posterior cingulate, precuneus in GM and posterior cingulate, thalamus and midbrain in WM, in addition, we also observed more pack-years smoking was associated with some certain smaller GM and WM volumes by ANCOVA. ConclusionYoung and middle-aged male smokers had many smaller brain areas than non-smokers. Some of these areas' volume had negative correlation with pack-years, while some had not. These may due to different pathophysiological role of smokings.