Mechanical loading is essential for bone development and prevention of age-related bone diseases. Muscular contractions during physical activity and the generated strain magnitude are primary determinants for the osteogenic response. However, the adaptation capacity of bones, especially due to different muscle contraction types, is largely unknown. In the present study we examined the effect of different running modes characterized by different muscle contraction types and loading patterns on the morphological, structural, and mechanical properties of different sites in the femur of growing rats. Thirty-six female Sprague-Dawley rats were randomly assigned to a nonactive age-matched control (AMC), a level running (LEVEL), and a 20° decline downhill running (DOWN) group (n = 12 each). Running groups were trained on a treadmill for 30 min/day, 5 days/week for 6 weeks. After death, pQCT analysis of the meta- and diaphyses, micro-CT analysis of the epiphysis, and mechanical testing of the femur were performed. The Tb.BMD in the metaphysis was significantly (P < 0.05) increased in the DOWN compared to the AMC group, whereas level running had no effect on Tb.BMD. While Young's modulus was significantly different (P < 0.05) between the DOWN and LEVEL groups, no structural alterations were found in the diaphysis between the groups. Further, subchondral trabecular bone did not show exercise-induced changes caused by the different running modes but displayed a remarkably high intraepiphyseal variability. Downhill running seems to be a potent osteogenic stimulus in the femoral metaphysis.