BACKGROUND: Physical activity may benefit health and reduce risk for chronic complications in normal and people with diabetes and peripheral vascular diseases. However, it is unclear whether leg muscle fatigue after weight-bearing physical activities, such as brisk walking, may increase risk for plantar tissue injury. In the literature, there is no evidence on the effect of muscle fatigue on plantar pressure after various walking intensities. The objectives of this study were to investigate the effects of various walking intensities on leg muscle fatigue and plantar pressure patterns. METHODS: A 3 × 2 factorial design, including 3 walking speeds (1.8 (slow and normal walking), 3.6 (brisk walking), and 5.4 (slow running) mph) and 2 walking durations (10 and 20 min) for a total of 6 walking intensities, was tested in 12 healthy participants in 3 consecutive weeks. The median frequency and complexity of electromyographic (EMG) signals of tibialis anterior (TA) and gastrocnemius medialis (GM) were used to quantify muscle fatigue. Fourier transform was used to compute the median frequency and multiscale entropy was used to calculate complexity of EMG signals. Peak plantar pressure (PPP) values at the 4 plantar regions (big toe, first metatarsal head, second metatarsal head, and heel) were calculated. RESULTS: Two-way ANOVA showed that the walking speed (at 1.8, 3.6, 5.4 mph) significantly affected leg muscle fatigue, and the duration factor (at 10 and 20 min) did not. The one-way ANOVA showed that there were four significant pairwise differences of the median frequency of TA, including walking speed of 1.8 and 3.6 mph (185.7 ± 6.1 vs. 164.9 ± 3.0 Hz, P = 0.006) and 1.8 and 5.4 mph (185.7 ± 6.1 vs. 164.5 ± 5.5 Hz, P = 0.006) for the 10-min duration; and walking speed of 1.8 and 3.6 mph (180.0 ± 5.9 vs. 163.1 ± 4.4 Hz, P = 0.024) and 1.8 and 5.4 mph (180.0 ± 5.9 vs. 162.8 ± 4.9 Hz, P = 0.023) for the 20-min duration. The complexity of TA showed a similar trend with the median frequency of TA. The median frequency of TA has a significant negative correlation with PPP on the big toe ( r = -0.954, P = 0.003) and the first metatarsal head ( r = -0.896, P = 0.016). CONCLUSIONS: This study demonstrated that brisk walking and slow running speeds (3.6 and 5.4 mph) cause an increase in muscle fatigue of TA compared to slow walking speed (1.8 mph); and the increased muscle fatigue is significantly related to a higher PPP.