Active commuting to and from school (ACS) has been recognized as a potential tool to improve physical fitness. Thus, this study aims to test the relationships between the average slope in the ACS and physical fitness, as well as to verify the mediator role of fatness in the relationship between average slope and physical fitness. A total of 257 participants, 137 boys and 120 girls, from 22 schools belonged to first and second High School grades participated in this study. Based on self-reported measure and Google Earth, participants were grouped into the active commuter (number of trips was ≥5, and the time of the trip was ≥15 min), mixed commuter (number of weekly trips was <5, and the time spent on the trip was <15 min) and passive commuter groups (those who reported traveling regularly by car, motorcycle, or bus). Specifically, in the active commuter group, a positive association between the average slope in the ACS with fatness was found, which in turn was positively related to strength lower limbs and cardiorrespiratory fitness. The average slope was not significantly associated with physical fitness indicators. Furtheremore, fatness did not mediate the relathionship between average slope and physical fitness. This research concluded positive associations between average slope and the body fat in the ACS. The tendency of findings signal that the average slope should be taken into account along with the distance, time and frequency of the active commuting.