Exercise training induces many adaptations in skeletal muscle, representative examples of which include an increase in the IIa myofibre and an increase in the capillary-to-fibre ratio (C:F ratio). Moreover, these phenomena are thought to be dependent on running distance. Ibuprofen is one non-steroidal anti-inflammatory drug that is often used as an analgesic, but its effect on skeletal muscle adaptation during endurance training is unclear. In the present study, therefore, we administered ibuprofen to mice during running wheel exercise for four weeks, and examined its effects on the increase in the IIa myofibre and the C:F ratio in skeletal muscle. We observed a significant increase of the IIa myofibre and C:F ratio even in the presence of ibuprofen. Moreover, in untreated mice, there was a significant positive and strong correlation between these parameters and running distance. These results indicate that the increase in the IIa myofibre and the C:F ratio in skeletal muscle usually depend on running distance. Interestingly, we observed no significant correlation between these parameters and running distance in ibuprofen-administered mice. Moreover, we found no significant increase of these parameters when the running distance was significantly increased, in comparison with untreated mice. These results indicate that ibuprofen administration during endurance training cancels running-distance-dependent adaptations in skeletal muscle. This suggests that even if ibuprofen administration facilitates longer-distance running, no further effects of training on skeletal muscle can be expected.