〔Abstract〕 Objective To investigate the effect of Apelin-13 regulation of VEGF/PI3 K/Akt signaling on femoral fracture healing. Methods Forty male SD rats were randomly divided into sham group, Model group, Apelin-13 low-dose group[Apelin-13 L, 25 μg/(kg·d)] and Apelin-13 high-dose group[apelin-13 H, 75 μg/(kg·d)], and 10 rats in each group. The model of femoral fracture was established and immediately treated with appropriate drugs for 4 weeks. Micro CT and X-ray were used to detect bone microscopic parameters and callus diameter. HE staining was used to observe bone tissue pathological changes. ELISA was used to detect the expression levels of serum bone markers BALP, PINP and osteoclast TRACP-5 b, CTX. qRT-PCR was used to detect VEGFA mRNA expression levels in callus tissues, and Western blot was used to detect the expression levels of related proteins in the VEGF/PI3 K/Akt signaling pathway in callus. Results Compared with the sham group, the Model group had severe pathological damage of femur and decreased femur bone density, tissue mineral density, bone mass fraction and X-ray score. BALP and PINP levels in serum decreased, while TRACP-5 b and CTX levels increased, and VEGFA mRNA, VEGFA, VEGFR2, PI3 K p85 and p-Akt expression levels in callus decreased. Compared with the Model group, the pathological injury of the femur in the Apelin-13 H group improved. Bone mineral density, tissue mineral density, bone volume fraction, X-ray score and callus diameter all increased. BALP and PINP levels in serum increased(P<0.05), while TRACP-5 b and CTX levels decreased, and VEGFA mRNA, VEGFA, VEGFR2, PI3 K p85 and p-Akt expression levels in callus increased. There was no significant difference between Apelin-13 L group and Model group(P>0.05). Conclusion Exogenous Apelin-13 can promote femoral fracture healing in rats, and its mechanism may be related to the activation of the VEGF/PI3 K/Akt signaling pathway.