Understanding complex systems is fundamental to understanding science. The complexity of science systems makes them very difficult to understand because they are composed of large number of variables with dynamic interdependencies that determines the behavior of the systems. Hence, understanding complex system requires students to build an accurate mental model of the system components depicting the causal interrelationships among them. Proponents of the inquiry-based science education argue that through the scientific method learner scan effectively build accurate mental models of the complex science systems and learn the deep principles that govern them. However, the literature on the effectiveness of inquiry learning has mixed results. Prior studies suggest that inquiry learning of complex systems calls for multivariate analysis, which requires high-level cognitive regulation skills to be effective. The goal of this study was to investigate the effect of learners' cognitive regulation skills on their understanding of complex systems during inquiry learning. Ninety ninth-grade students were provided with a complex problem task that called for their understanding of a complex lake ecology system in the context of a simulation-based inquiry-learning environment. Findings confirmed the crucial importance of cognitive regulation during inquiry learning. In addition, results suggested that task complexity was an important factor affecting cognitive regulation of inquiry processes, which may have implications for designing cognitive regulation scaffolds.