This study investigated knowledge practice and challenges of Junior High School Science teachers in Differentiated Instruction (DI) in Kpandai District of the Northern Region of Ghana. The study employed the concurrent nested design. Out of 268 teachers, a sample size of 31 science teachers was drawn to participate in the study through questionnaire and a sub-sample of five teachers was purposively selected for interviews. The quantitative data was analysed using descriptive statistics while the qualitative data was analysed thematically. The study concluded that most JHS science teachers in Kpandai District possessed required knowledge on DI and they actually differentiated the instruction in their Science classes. However, they faced some challenges when differentiating their instructions. The study recommends that knowledge of DI possessed by most Science teachers should be strengthened through regularly organizing in-service training for them. This should be done by GES Directorate of Kpandai to enable the teachers improve their knowledge of DI. Teachers should be supported by SISOs to practice every aspect of DI especially when assessing the learners. Finally, the government and other educational stakeholders should ensure that textbooks and other materials/resources are readily made available to Science teachers for effective implementation of DI in schools.
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