Objective: The association between neighborhood disadvantage and health is well-documented. However, whether these associations may differ across rural and urban areas is unclear. This study examines the association between a multi-item neighborhood social and economic environment (NSEE) measure and diabetes prevalence across urban and rural communities in the US. Methods: This study included 27,159 Black and White participants aged ≥45 years at baseline (2003–2007) from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Each participant's residential address was geocoded. NSEE was calculated as the sum of z-scores for six US Census tract variables (% of adults with less than high school education; % of adults unemployed; % of households earning <$30,000 per year; % of households in poverty; % of households on public assistance; and % of households with no car) and within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). NSEE was categorized as quartiles, with higher NSEE quartiles reflecting more disadvantage. Prevalent diabetes was defined as fasting blood glucose ≥126 mg/dL or random blood glucose ≥200 mg/dL or use of diabetes medication at baseline. Multivariable adjusted Poisson regression models were used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for the association between NSEE and prevalent diabetes across community types. Results: The mean age was 64.8 (SD=9.4) years, 55% were women, 40.7% were non-Hispanic Black adults. The overall prevalence of diabetes was 21% at baseline and was greatest for participants living in higher density urban areas (24.5%) and lowest for those in suburban/small town areas (18.5%). Compared with participants living in the most advantaged neighborhood (NSEE quartile 1, reference group), those living in the most disadvantaged neighborhoods (NSEE quartile 4) had higher diabetes prevalence in crude models. After adjustment for sociodemographic factors, the association remained statistically significant for moderate density community types (lower density urban quartile 4 PR=1.50, 95% CI=1.29, 1.75; suburban/small town quartile 4 PR=1.54, 95% CI=1.24, 1.92). These associations were also attenuated and of smaller magnitude for those living in higher density urban and rural communities. Conclusion: Participants living in the most disadvantaged neighborhoods had a higher diabetes prevalence in each urban/rural community type and these associations were only partly explained by individual-level sociodemographic factors. In addition to addressing individual-level factors, identifying neighborhood characteristics and how they operate across urban and rural settings may be helpful for informing interventions that target chronic health conditions.