The purpose of this research is threefold: (1) to identify the difficulties that Grade 10 students in a Lebanese school have that hinder their conceptual understanding at the micro-macro-symbolic interface in chemistry, (2) to investigate the effect of a macro-micro-symbolic teaching approach on students' relational understanding of chemical reactions, and (3) to characterize students' conceptual profiles regarding their understanding of chemical reactions in terms of macro, micro, symbolic levels and the relations among them, at the end of the teaching sequence. Forty six 10th graders from two sections participated in the study. A student-centered approach was followed in both sections based on constructivist pedagogy. Hence the teacher played the role of a facilitator who guided students in a meaning making inductive learning process, through questioning, monitoring, validating, and clarifying ideas. Instruction in the experimental group was characterized by macro-micro-symbolic teaching that focuses on the interplay between the levels, integrates various representations, and engages students in an epistemic discourse about the nature of knowing in chemistry. Data sources for the study included a pre-test and two post-intervention tasks: a post-test and a concept map task, in addition to interviews with selected students from both sections. Findings indicated that macro-micro-symbolic teaching enhanced students' conceptual understanding and relational learning of chemical reactions. Besides, four assertions related to students' conceptual and epistemological thinking in response to the different teaching approaches are presented. Implications for instruction and for teacher education programs, as well as recommendations for further research, are discussed in light of these findings. (Contains 5 tables and 5 figures.)