Objective To study the effects of aerobic exercise combined with curcumin on insulin resistance and liver pathological changes in ob / ob diabetic mice, to determine the effects of curcumin combined with aerobic exercise on the hepatic fatty acid β-oxidation signal pathway, and to explore the specific mechanisms behind these effects. Methods Thirty-two ob / ob diabetic mice were divided into a diabetic control group (ON group), aerobic exercise intervention group (OA group), curcumin intervention group ( OC group), and aerobic exercise + curcumin intervention group ( OAC group), while another eight C57 / BL6J mice served as a normal control group (NC group). During the experiment, aerobic exercise training was performed on OA group and OAC group mice. Curcumin treatment (50 μg / (g·d)) was applied to OC group and OAC group mice. After 8 weeks of intervention, glucose tolerance and insulin resistance of the mice were determined. The pathological changes and fatty acid β-oxidation signaling pathways in the liver were also measured. Results After the experimental intervention, the insulin sensitivity of the OA group, OC group, and OAC group was significantly increased, and the OAC group almost reached the level of the NC group; the serum TC and TG of the OA group, OC group, and OAC group were lower than those of the ON group, and the liver function was significantly improved; the liver fibrosis level of diabetic mice was significantly improved, and these levels of the OA group, OC group, and OAC group were significantly lower than those of the NC group. There was no significant difference between the OAC group and the NC group in the diabetic control group. There was also no significant change in the expression of fatty acid synthesis-related genes in the liver, but the expression of fatty acid β-oxidation-related genes in the OA group, OC group, and OAC group was significantly higher than that in the ON group, and the expression of fatty acid β-oxidation-related genes in the OAC group was significantly higher than that in the OA group and OC group. Western blotting showed that the fatty acid β- oxidation pathway in the liver of the OA group, OC group, and OAC group. The expression of carnitine palmityl transferase I (CPT-I) was significantly higher than that in the ON group. Conclusions Aerobic exercise combined with curcumin can promote the expression of the rate-limiting enzyme CPT-I involved in fatty acid β-oxidation in the liver of diabetic mice, thereby promoting fatty acid β-oxidation to enhance lipid decomposition, improving pathological changes in the liver and enhancing insulin sensitivity. These result may provide new ideas for the treatment of diabetes.