This study sought to determine the significant relationship between student attributes (background knowledge, readiness, interests, and learning profiles) and the teachers' use of DI elements (content, process, product, and learning environment differentiation) in primary and middle schools of Enjibara and Chagni town administrations of Awi zone, Ethiopia. A total of 364 randomly selected teachers were part of this study. The measurement scale has 27 items, and the Cronbach's alpha (a) estimates for internal consistency reliability were ranging from 0.80 to 0.93. Convergent and discriminant validities of the constructs were established. Standardized factor loadings from CFA were ranging from 0.65 to 0.81. The study affirmed that variation in students' attributes has a strong direct influence on content and learning environment differentiations. Differentiating content has a stronger direct influence on process differentiation. Likewise, process and learning environment differentiations have stronger direct influence on product differentiation. Moreover, mediation analyses showed that variation in students' attributes has indirect effect on product differentiation via process and learning environment differentiations. Also, process differentiation has fully mediated the influence of content differentiation and partially mediated the influence of learning environment differentiation on product differentiation. In conclusion, this study provides strong evidence on the direct and indirect influence of variation in students' attributes on differentiated instruction by applying more advanced approach of structural equation modeling. In order to address the student attributes, varying the contents and learning environments need to give priority than varying the process and the product.