The purpose of the present study was to investigate whether genetic differences in muscle histochemical characteristics were related to the voluntary wheel-running activity level by using genetically fast-twitch fiber-dominant rats (FFDR) and control rats (CR). The rats were divided into four groups; sedentary CR (Sed-CR), wheel-running CR (WR-CR), sedentary FFDR (Sed-FFDR), and wheel-running FFDR (WR-FFDR). Wheel access was started at age 9 wk and lasted for 7 days. The FFDR showed a lower percentage of type I fibers of the deep portion of gastrocnemius and soleus muscles and a higher percentage of both type IIX fibers of the gastrocnemius muscle and type IIA fibers of the soleus muscle compared with CR. A higher capillary density and smaller fiber cross-sectional area were also observed in FFDR. The daily running distance in WR-FFDR was higher than in WR-CR for each 7 days. The total running distance for 7 days in WR-FFDR was 3.2-fold higher than in WR-CR. On day 7 of the 7-day test, the total number of active 1-min intervals for 24 h, the average rpm when they were active, and the maximum rpm for any single 1-min period in the WR-FFDR were significantly higher than in the WR-CR (1.5-, 2.9-, and 2.0-fold, respectively). These results suggest that mechanical or physiological muscle characteristics may thus affect the wheel-running activity level.