Americans' distrust in the health care system has increased in the past decades; however, little research has explored the impact of distrust on self-rated health and even less is known about whether neighborhood social environment plays a role in understanding the relationship between distrust and self-rated health. This study fills these gaps by investigating both the direct and moderating associations of neighborhood social environment with self-rated health. Our analysis is based on the 2008 Philadelphia Health Management Corporation's household survey and neighborhood-level data. Findings from multilevel logistic regression show that after controlling for individual- and neighborhood-level covariates, distrust is directly and adversely related to self-rated health, and that neighborhood social affluence and stability are directly and negatively associated with the odds of reporting poor/fair health. Neighborhood disadvantage and crime rates are not directly related to self-rated health, but increase the odds of having poor/fair health via distrust. Overall, our results suggest that macro-level actions can alter individual's perception of residential environment and lead to improved health. To improve the public health in an urban setting, rebuilding confidence in the health care system is integral, and the policies that help establish safe and cohesive neighborhoods may reduce the adverse effect of distrust on self-rated health.