Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice. They were acclimatised to feeding for one week and randomly divided into control (D) group, tumour (M) group, exercise preconditioning group (QAM) group, lifetime exercise (AM) group and exercise (HAM) group, 7 mice in each group.The QAM and AM groups were subjected to aerobic exercise regimen in the 2-6 weeks group.1 At week 7, 0.2 ml of CT26 colon cancer cell suspension was injected subcutaneously into the back of the left hind limb of the experimental group mice, and 0.2 ml of saline was injected at the same location in the control group mice. In 7-9 weeks, AM group and HAM group were subjected to aerobic exercise regimen 2. In the experiments, the mice living status and skeletal muscle mass and function were examined, and at the end of the experiments, samples were taken to detect the cross-sectional area of gastrocnemius muscle fibres (CSA) by HE staining, and the expression of proteins related to synthesis and catabolism of thanatopathic gastrocnemius muscle was examined by Western blot method.Results (1) There was no significant change in the body weight of mice among all groups, but the gastrocnemius muscle weight ratio was significantly lower in the M, QAM, and HAM groups compared with that in the D group ; and it was significantly increased in the AM group compared with that in the M, QAM, and HAM groups. (2) The food consumption endpoints showed that Group D > Group M > Group HAM > Group AM > Group QAM. (3) Grip strength, skeletal muscle circumference, and CAS were significantly reduced in each group of mice M, QAM, AM, and HAM compared with group D; and compared with M, QAM groups, the grip strength of mice in the HAM group was significantly increased; compared with the M group, the CAS of mice in the QAM, AM, and HAM groups were significantly increased ; compared with the QAM and HAM groups, the CAS of mice in the AM group was significantly increased ; and compared with the D group, the CAS of M group had a significant decrease in endurance ; compared with M group, QAM, AM and HAM groups had a significant increase in endurance . (4) Compared with group D, MURF1 protein expression level was significantly decreased in M, QAM, AM, and HAM groups ; compared with group M, MURF1 protein expression level was significantly decreased in AM and HAM groups; and compared with group QAM, MURF1 in HAM groups protein expression level was significantly decreased. Among them, MAFbx/Atrogin-1 protein expression level was not significant in all groups. (5) Compared with group D, FNDC5 protein expression was significantly decreased in group M; compared with group QAM, it was significantly decreased in group HAM , and there was no significant change in FNDC5 protein expression in other groups. (6) Compared with M group, PGC-1α protein expression was significantly lower in QAM and HAM groups. (7) Compared with groups D and M, p-AMPK/AMPK and p-AMPK protein expression was significantly increased in QAM group ; compared with QAM group, p-AMPK protein expression was significantly decreased in AM and HAM groups . AMPK protein expression was significantly decreased in the QAM, AM, and HAM groups compared with the D group . Conclusion Lifelong and pre-tumour inoculation aerobic exercise improves skeletal muscle mass and function in colon cancer-loaded mice, which may be due to the activation of APMK phosphorylation by exercise, which stimulates the skeletal muscle itself to secrete FNDC5 to regulate MuRF1 protein expression.