The goal of aptitude-treatment interactions (ATIs) is to find the interactions between treatments and learners' aptitudes and therefore to achieve optimal learning. This study aimed at understanding whether the aptitudes of meaning-making, self-regulation, and knowledge management (KM) would interact with the treatment of 17-week KM-based training and then influence creativity in e-learning. The participants were 31 university students, and all variables were measured using online systems. ATIs and mediation effects during the training were found. Specifically, while meaning-making indirectly influenced creativity via KM, self-regulation influenced creativity both directly and indirectly via KM; moreover, university students with higher level of KM and self- regulation ability benefited more from the training than their counterparts. This study not only sheds lights on understanding how ATIs influence creativity learning, but also provides a new approach--KM-based training--to improve university students' creativity in environments of e-learning.