Low-intensity pulsed ultrasound (LIPUS) has been shown to have many benefits, such as inhibiting inflammation, stimulating cell proliferation and differentiation, promoting angiogenesis, and so on. So, can exercise fatigue induced liver inflammation be effectively relieved by LIPUS? If possible, what is the possible mechanism? This study first investigated the effect of different intensity exercise on liver inflammation. Rats were divided into three groups: normal control group, exercise fatigue group, and aerobic exercise group. The results showed that aerobic exercise increases both anti-inflammatory factors and pro-inflammatory factors, while fatigue exercise decreases anti-inflammatory factors and increases pro-inflammatory factors, leading to severe liver injury and fibrosis. Then, we investigated the therapeutic effect of LIPUS on liver inflammation caused by exercise fatigue. Starting from the 6th week, the liver was irradiated with LIPUS of 80 mW/cm2 for 20 min/d after daily exercise for 7 weeks. The results showed that LIPUS significantly decreased liver injury and fibrosis, significantly up-regulated the expression of STAT6, IL-13, and its receptors IL-13Rα1, and down regulated the expression of NF-κBp65 in exercise fatigue rats. These results indicate that LIPUS can reduce fatigue-induced liver inflammation, and the mechanism is related to the regulation of the IL-13/STAT6/NF-κBp65 pathway.