Integrating both proactive and reactive risk-mitigation mechanisms, this research constructs a bi-level network design problem for hazardous materials (hazmats) to regulate the carriers' use of roads, such that the environmental impact is minimized. In more detail, by embedding the emergency response time into the risk assessment, the locations of hazmat response teams are determined along with toll schemes, road closures, and new road constructions. The uncertainties of demand, including differences in the number of shipments, origin/destination changes, and amount variations, are also taken into account by applying a scenario-based approach. The proposed bi-level model is first solved optimally by a single-level reformulation, and then by a three-stage heuristic method for larger instances. Through numerical experiments on a real-world road network in Nanchang, a city in China, a set of management insights are derived to facilitate policy-making in regulating hazmat transportation.