Institutions managing European Funds are obliged by the European Commission to evaluate them. In the article, a micro-macroeconomic model of the regional value-creation system with the impact of structural funds is proposed. Besides the traditional variables of supply and demand in the economy, the model also embraces variables reflecting natural environment protection as well as research and development and innovation. The model may be used as a theoretical framework for evaluation with the usage of quantitative and qualitative methods. The model is based on a systems approach that emphasizes interdependencies and causal loops rather than unidirectional causal relationships. An application of the model for the evaluation of the impact of European Funds on Polish counties is presented, showing the positive impact of the funds of the 2014-2020 programming period on an income proxy and knowledge-based entrepreneurship.