Purpose: Research has provided powerful evidence that what teachers do in the classroom matters most for the learning of students. Evidence also suggests that school leaders can make a significant difference to student learning via their influence on teachers' attitudes, beliefs and classroom practices. The purpose of this study was to examine if/how principal instructional leadership practices affect differentiated instruction in Omani schools, and understand the role that teacher collaboration and self-efficacy play in this dynamic. Design/methodology/approach: The study used structural equation modeling (SEM) to analyze data collected from a sample of 496 teachers working in public schools in Muscat, Oman. Findings: The findings revealed no direct association between principal instructional leadership and differentiated instruction. Instead, the effects of principal instructional leadership on differentiated instruction were achieved indirectly through the mediation of teacher collaboration and teacher self-efficacy. Collaboration was also found to have a positive influence on the teachers' self-efficacy beliefs. Originality/value: The significance of this study stems from its relevance to the educational developments unfolding not only in Oman, but in the Gulf region at large. Recent reviews of educational administration and leadership research in the Gulf states indicate the scarcity of empirical research investigating the relationship between principal leadership and teacher practices. This is problematic as it creates a gap in our knowledge of the factors that can support ongoing school improvement initiatives in the region. More specifically, we expect our findings to guide current educational reforms aimed at raising education quality via promoting effective teaching and learning in Omani schools.