The entrepreneurship has a major role in the economic development of a country and also for job creation and innovation. The entrepreneurial activity is influenced by many factors, understanding and examining these factors is very important for identifying the adequate measures that can support and develop the entrepreneurial activity. The economic recession and the significant increase in unemployment, in the context of the recent economic crisis, have renewed the researchers' interest on the role of entrepreneurship and its determinant factors. Starting from those stated above, through this paper, we aim to empirically identify the key macroeconomic and business environment factors that have an impact on the dynamics of entrepreneurial activity and evaluate their influence in the EU countries, for the period 2002-2015. As independent variables, we took into account 14 macroeconomic indicators and of the business environment that could have an impact on the entrepreneurial activity. The results of the empirical research indicate that a large part of the independent variables has a significant impact on entrepreneurial activity in line with the results of other empirical studies. Thus, the dynamics of entrepreneurial activity is significantly influenced by the annual percentage growth rate of GDP and GDP per capita, tax rates, fear of failure, entrepreneurial Intentions, perceived capabilities, perceived opportunities and cost of business start-up procedures. Overall, identification and knowledge of key macroeconomic and business environment factors that influence entrepreneurial activity are of interest to decision makers at various levels in order to adopt and implement appropriate measures that stimulate and promote entrepreneurship.