There is a stringent necessity in Romania to reconsider the role of entrepreneurship in regional development and to increase awareness regarding the importance of encouraging female entrepreneurship. Women entrepreneurs are in the minority in Romania, as they are generally in Europe. The gender gap is obvious according to the different definitions of entrepreneurship: new venture creation, business ownership, and self-employment. The paper describes some basic facts about the differences between men and women entrepreneurs in the six counties of western Romania (Maramures, Satu-Mare, Bihor, Arad, Timis, Caras Severin) compared with the rest of Romania, and other countries from the EU, focusing on gender differences in evolution, structure, density of SMEs sector, industry composition, human capital, social capital, preferences, motivations etc. and identifies some potential explanations in order to promote female entrepreneurship. Starting from here, the present paper proposes gender-sensitive regional strategies in encouraging female entrepreneurship to exploit the possibilities offered by local and regional potential taking into account opportunities, difficulties and constraints in the SMEs sector during times of economic crisis. The paper presents research results from the project entitled Entrepreneurship and the Equal Opportunities. An Inter-regional Model of Women's School of Entrepreneurship. This project, financed by the European Social Fund with funding of over 3.5 million Euros, is the first strategic project in the field of human resources development in Romania that promotes female entrepreneurship. The area covered by the project is the western part of Romania, and includes Maramures, Satu-Mare, Bihor, Arad, Timis, and Caras Severin counties, being implemented by partner universities from each of these counties. The general objective is to promote equal opportunities in the field of entrepreneurship, by stimulating the desire of women, especially those coming from rural areas, to initiate and develop their own business in the context of sustainable development in their communities. The target group is formed of 1,800 women, both from urban and rural areas, from the north-west and western regions of Romania.