Natural gas supply chain is potentially susceptible to high costs caused by horrible outcomes such as explosion, injuries and mortality of workers, greenhouse gas emissions and production process halt. Macro-ergonomics analysis and design method is an efficient methodology which can lead to an overall gas supply chain optimization. This study presents a novel concept of macro-ergonomics analysis and design method, in form of a multi-objective mathematical model. Problem objectives include reducing operating and transportation costs, environmental costs, and delay costs besides increasing in value of purchasing from importers. Results of the mathematical model in form of a multi-objective optimization, were obtained through augmented e-constraint method. The model have been applied this in the supply chain of Iran gas transmission which is one of the country's most sensitive and vital industries. Results of the model were analyzed after implementing the suggestions of macro-ergonomics approach to evaluate the considered supply chain performance, and the result shown 10% reduction in operating costs per unit. This study can be entitled the first research which evaluates the macro-ergonomics analysis and design method trough mathematical model supply chains. (C) 2016 Elsevier Ltd. All rights reserved.