Background: Resistance wheel running (RWR) can promote resistance-like training adaptations in mouse skeletal muscle (SkM), but its endurance-training effects are lesser known. Methods: Voluntary RWR was modulated as an exercise model to increase mouse hind-limb plantar-flexor torque and to promote endurance-training adaptations. Thirty male mice (cohort 1, n= 16; cohort 2, n= 14), were trained on a prototype RWR system that applied resistance relative to body mass (BM). Mice were sequentially, (1) screened for running ability (screening; 3-days); (2) trained with incremental adjustments to wheel loads (pre-training; 8-weeks); (3) grouped into cage-activity only (CA), and constant Low-0%, Med-15%, or High-25% BM resistance conditions (static training; 5-weeks); (4) trained with resistance adjusted in real-time (dynamic training; cohort 1, 7-weeks; cohort 2, 10-weeks); and (5) sacrificed for various assays. Plantar-flexor torque was determined during each training phase. After dynamic training, resistance runners in each cohort were sub-grouped post-hoc by work tertiles. Results: Wheel running distance varied between cohorts (cohort 2 > 1). During dynamic training, wheel running (±added-resistance) improved plantar flexor torque normalized to BM by 19% only in cohort 2 (p= 0.007). Muscle mass and cross-sectional area were unchanged. Runners in both cohorts (±added-resistance) improved maximal running capacity vs. CA-controls (+69% and +115%; both p < 0.05), but metabolic training adaptations were less evident. Conclusions: Wheel running promoted SkM strength and endurance, but there was a greater increase in endurance capacity than strength. This outcome may be due to adaptive signaling interference. / Master of Science