Background: According to recent research studies, the built and socioeconomic contexts of neighborhoods are associated with African American adolescents' participation in physical activity and obesity status. However, few research efforts have been devoted to understand how African American adolescents' perceptions of their neighborhood environments may affect physical activity behaviors and obesity status. The objective of the current study was to use a perceived neighborhood disorder conceptual framework to examine whether physical activity mediated the relationship between perceived neighborhood disorder and obesity status among African American adolescents. Methods. The data were obtained from a cross-sectional study that examined social and cultural barriers and facilitators of physical activity among African American adolescents. The study included a sample of 101 African American adolescents age 12 to 16 years and their parents who were recruited from the Birmingham, Alabama metropolitan area. The primary outcome measure was obesity status which was classified using the International Obesity Task Force cut off points. Moderate-to-vigorous physical activity was assessed via accelerometry. Perceived neighborhood disorder was assessed using the Perceived Neighborhood Disorder Scale. Mediation models were used to examine whether the relationship between neighborhood disorder and obesity status was mediated by physical activity. Results: Perceived neighborhood disorder was significantly and positively related to obesity status and moderate-to-vigorous physical activity was inversely associated with obesity status. However, there was no evidence to support a significant mediating effect of moderate-to-vigorous physical activity on the relationship between neighborhood disorder and obesity status. Conclusion: Future studies should longitudinally assess perceived neighborhood disorder characteristics and childhood adiposity to examine the timing, extent, and the mechanisms by which perceived neighborhood disorder characteristics increase the risk of obesity. © 2013 Dulin-Keita et al.; licensee BioMed Central Ltd.