Abstract: Objective: To explore whether peripheral blood levels of cognition-related proteins play a mediator role in the impact of physical activity on cognitive abilities. Methods: A total of 306 participants recruited (boys 176;girls 130) from 7 kindergartens in Shanghai. Participants' physical activity was assessed using Acti Graph GT3X⁺accelerometer (GT3X⁺, Acti Graph, Pensacola, FL, USA) , "China- Wechsler Abbreviated Intelligence Scale for children (C- WAISC) " (City version) was used to examine the cognitive abilities, ELISA (Enzyme-linked Immunosorben Assay, ELISA) and R & D System (Human IGF-1 Quantikine ELISA Kit;Human BDNF Quantikine ELISA Kit, U.S.) kit were used to detect the concentrations of IGF-1 and BDNF. Results: A total of 174 preschoolers (boys 97;girls 77) among 306 participants have the complete data of level of physical activity, cognitive ability tests and peripheral cognition- related proteins. Regardless of the results of the regression analysis of the boys or girls, the results did not support the hypothesis that peripheral blood levels of IGF-1and/or BDNF play a mediator role in the impact of physical activity on cognitive abilities. Conclusions: The results from our study did not find the mediator effect of peripheral blood IGF-1 and/or BDNF on the association between physical activity and cognitive abilities.