To observe the effect of moxibustion on cancer-related fatigue(CRF) and the AKT-NF-κB signaling pathway.Methods:A total of 55 BALB/C mice were randomly divided into blank group(n=10)，control group(n=15)，moxibustion group(n=15) and infrared group(n=15).The blank group received no treatment，while the control group was given subcutaneous transplantation of 4T1 breast cancer cell line combined with cisplatin to construct a CRF model.The moxibustion group and the infrared group were treated with moxibustion and infrared irradiation，respectively at Guanyuan(CV 4) of CRF mice for 4 weeks.After intervention，the behavior of mice(treadmill fatigue test and tail suspension test) was observed，and enzyme linked immunosorbent assay(ELISA) was used to detect the serum level of interleukins(IL-1β，IL-6，and IL-10).Immunofluorescence was used to determine the expression of IL-6 in spleen.Reverse transcription-polymerase chain reaction(RT-PCR) was performed to determine the mRNA expressions of IL-6 and NF-κB p65 in tumor tissues，and the protein expressions of AKT，p-AKT，NF-κB p65 and p-NF-κB p65 in tumor tissues were detected by Western blot.Results:Compared with the blank group，the control group presented shortened treadmill time and distance，decreased IL-10，increased number of electric shocks，prolonged tail suspension time，and elevated serum levels of IL-1β and IL-6 and expression of IL-6 in spleen.Compared with the conditions in the control group，the treadmill time and distance and IL-10 were increased，and the number of electric shocks，tail suspension time，elevated serum levels of IL-1β and IL-6 and up-regulated expression of IL-6 in spleen; the mRNA expressions of IL-6 and NF-κB p65 as well as the expressions of p-AKT and p-NF-κB p65 in the intervention groups were decreased.The infrared group had shorter tail suspension time and lower serum levels of IL-6 and p-NFκB p65 than the moxibustion group.Conclusion:Moxibustion can improve CRF via the mechanism of down-regulating AKT-NF-κB signaling pathway，and infrared is an important factor for the efficacy of moxibustion.