For the last two decades, a number of policies aimed at increasing participation of female students in higher education have been implemented by Uganda Government. However, the participation of female students in the engineering courses in Makerere University, Uganda’s biggest University, has remained between 17% to 20% only. Furthermore, over 90% of the female engineering students are from the ‘elite’ and advantaged urban schools located in the capital city, Kampala, and its surrounding Districts of Mukono and Wakiso. Rural secondary schools perform poorly in Physics and Mathematics; the key technology and engineering subjects. One rural District, which has failed to send female students to Makerere University for engineering training, is Arua- a remote, poor and insecure District in the West Nile Region of Uganda. The main objective of the doctoral research was to improve the performance in Physics and Mathematics, at Advanced Level Examinations, of two rural girls’ secondary schools in Arua (Muni and Ediofe) through application of e-learning. Both schools have no functional science laboratories and libraries. They also have no qualified and committed teachers who can competently teach at that level of education. The research included participatory action research methodology and the use of interactive multimedia CD-ROMs for Physics and Mathematics as the main course delivery platform. During the study, twenty nine female students from the two schools effectively used the hybrid e-learning tools and applications for six months in 2007 and they were independently examined four times. The repeated measures data that were collected were analysed using multilevel methods to establish the effects of the hybrid e-learning intervention and school contexts on the performance of the students in external examinations. Results of the analysis showed that, 41% of the students passed and were eligible for university admission. Furthermore, it was found that within-student factors were chiefly responsible for the performance of students in Physics, while for Mathematics, the school contexts were more dominant. However, after extrapolation of the performance of the students over twelve months, up to 72% of the students would have passed and be eligible to join higher institutions of learning. The study, which focused e-learning for two schools in the rural district of Arua, included co-evolving elements in a Triple Helix Processes. The results were the setting up of the ICT/GIS Research Centre in Arua. The Centre is not only helping the community in the West Nile region of Uganda but also near by communities in Southern Sudan and Eastern Democratic Republic of Congo. The Centre has helped to establish an Information Society in the region.