The cardiovascular and stroke mortality rates in Arkansas are among the highest in the USA. The annual trends of stroke and cardiovascular mortality are barely correlated to smoking cessation; while the prevalence of risk factors such as obesity; cholesterol and hypertension increased over the 1979-2007 period. The study determined the effect of chronic exposure to PM2.5 on non-accidental; cardiovascular; stroke and lung cancer mortality in Arkansas over the 2000-2010 period using the World Health Organization's log-linear health impact model. County chronic exposures to PM2.5 were computed by averaging spatially-resolved gridded concentrations using PM2.5 observations. A spatial uniformity was observed for PM2.5 mass levels indicating that chronic exposures were comparable throughout the state. The reduction of PM2.5 mass levels by 3.0 μg/m3 between 2000 and 2010 explained a significant fraction of the declining mortality. The effect was more pronounced in southern and eastern rural Arkansas as compared to the rest of the state. This study provides evidence that the implementation of air pollution regulations has measurable effects on mortality even in regions with high prevalence of major risk factors such as obesity and smoking. These outcomes are noteworthy as efforts to modify the major risk factors require longer realization times. © 2014 by the authors; licensee MDPI, Basel, Switzerland.