Aim of the study: The present study aims to compare the cytological changes of exfoliated epithelial cells taken from different oral sites of smokers and non-smokers patients and to compare the polymorph nuclear leucocytes obtained from salivary samples of the studied groups.A total of 200 patients selected from the Out Patient Clinic of the Department of Oral Medicine, Faculty of Oral and dental Medicine, Cairo University.These patients classified into 2 groups:Microscopical examination Cytological evaluation: I ) Non smoker (control group) The cytological examination of hematoxylin and eosin stained smears obtained from different sites (gingiva, tongue, palate and cheek) of oral mucosa of non smoker individuals revealed normal cellular pattern some of which resembling the squamous cells of the prickle cell layer having polyhedral outline with almost rounded to oval lightly stained nuclei (fig. 2 ). Other cells resembling the flattened cells of the granular cell layer were also noted these cells showed spindle outline with spindle nuclei (fig. 3). The examination also revealed few inflammatory cell infiltration (fig.3) with few polymorph nuclear leukocyts (fig.4). II) Smoker: The cytological examination of hematoxylin and eosin stained smear obtained from different sites (gingiva, tongue, palate and cheek) of oral mucosa of smoker individuals revealed polyhedral or squamous cells, most of them showed darkly stained nuclei which appear to be small and pyknotic (fig.4). Dense inflammatory cells infiltration (fig.5) Based upon the results of the present study it could be concluded that smoking has a potential harmful effect on oral mucosa possibly via nuclear changes that suggested induction of apoptosis.Smoking has a direct stimulatory effect on leucocytes proliferation leading to increased number of PNLs in saliva.