Recent studies have suggested role of diabetes mellitus in the development of periodontal diseases, oral inflammatory and neoplastic lesions. We analysed data from randomised oral cancer screening trial in Kerala, India, to study the association between chronic diseases in general, diabetes mellitus in particular, and pre-malignant oral lesions and conditions. A total of 927 subjects with oral leukoplakia, 170 with oral submucous fibrosis, 100 with erythroplakia lesions and 47,773 apparently healthy subjects constituted the cases and controls respectively for our present study. The odds ratio (OR) for oral leukoplakia among women with a history of diabetes mellitus was found to be 2.0 (95% confidence interval (CI) = 1.4–2.9) whereas that for erythroplakia was 3.2 (95% CI = 1.3–7.9), after adjusting for potential confounders. No statistically significant association between diabetes mellitus and oral submucous fibrosis and pre-cancerous lesions/conditions in men was found. An association between diabetes mellitus and pre-malignant oral lesions among women has been observed in our study, although the underlying mechanisms are not clear. This needs to be further evaluated in other settings. © 2005 Wiley-Liss, Inc.