This article investigates the relationship among objectively assessed neighborhood socio-economic status (SES), subjective perceptions of neighborhood environment, individual SES and psychosocial factors, and self-rated health among middle-aged and older adults. Analysis of data from a representative sample of adults, aged 50-67 years in Cook County, Illinois, shows a significant association between objective neighborhood SES and self-rated health after controlling for age, gender, and race/ethnicity, but the effect is substantially explained by individual SES and neighborhood perceptions. By contrast, perceived neighborhood quality (i.e., subjective ratings of neighborhood physical, social, and service environments) exhibits a significant effect after controlling for individual socio-demographic factors as well as neighborhood SES. In turn, the effects of perceived neighborhood environment on health are partially explained by the psychosocial factors of loneliness, depression, hostility, and stress, but not by perceived social support or social networks. In sum, the research supports a model in which the effects of neighborhood SES on self-rated health act through sequential pathways of individual SES, perceptions of neighborhood quality, and psychosocial status.