Background: Existing prevention and treatment strategies target the classic types of diabetes yet this approach might not always be appropriate in some settings where atypical phenotypes exist. This study aims to assess the socio-demographic and clinical characteristics of people with diabetes in rural Rwanda compared to those of urban dwellers. Methods: A cross-sectional, clinic-based study was conducted in which individuals with diabetes mellitus were consecutively recruited from April 2015 to April 2016. Demographic and clinical data were collected from patient interviews, medical files and physical examinations. Chi-square tests and T-tests were used to compare proportions and means between rural and urban residents. Results: A total of 472 participants were recruited (mean age 40.219.1years), including 295 women and 315 rural residents. Compared to urban residents, rural residents had lower levels of education, were more likely to be employed in low-income work and to have limited access to running water and electricity. Diabetes was diagnosed at a younger age in rural residents (mean ± SD 32±18 vs 41±17 years; p < 0.001). Physical inactivity, family history of diabetes and obesity were significantly less prevalent in rural than in urban individuals (44% vs 66%, 14.9% vs 28.7% and 27.6% vs 54.1%, respectively; p < 0.001). The frequency of fruit and vegetable consumption was lower in rural than in urban participants. High waist circumference was more prevalent in urban than in rural women and men (75.3% vs 45.5% and 30% vs 6%, respectively; p< 0.001). History of childhood under-nutrition was more frequent in rural than in urban individuals (22.5% vs 6.4%; p< 0.001). Conclusions: Characteristics of people with diabetes in rural Rwanda appear to differ from those of individuals with diabetes in urban settings, suggesting that sub-types of diabetes exist in Rwanda. Generic guidelines for diabetes prevention and management may not be appropriate in different populations.