This study was designed to examine teachers' self-efficacy as a potential mediator to understand the relations between innovative school climate and implementation of cognitive activation strategies during instructional practice. The data of this study are derived from the 2018 Teaching and Learning International Survey (TALIS) conducted by the OECD. This study was based on a sample of 2287 Korean teachers from 176 middle schools. Multi-level mediation analyses with Monte Carlo confidence intervals were used to measure within-subject effects at the teacher level (L1) and between-subject effects at the school level (L2). In this study, a 2-1-1 model containing a level-2 X variable and level-1 M and Y variables were designed. First, the author analyzed the relations between the variables and tested the mediation effect using the MLmed Macro for SPSS with robust standard errors (REM estimation). The results of multi-level mediation analyses were supportive of a hypothesized conceptual framework. First, the results show significant effects of the innovative school climate on the teachers' self-efficacy and implementation of cognitive activation strategies respectively at the school level. Second, the higher the innovative school climate, the more implementation of cognitive activation strategies, and this relationship were mediated by teachers' self-efficacy. Based on these results, the researcher suggested strategies for teachers to implement cognitive activation practices.