Objective To investigate the effect of AKT/mTOR and JAK/STAT pathways co-activation on axon regeneration and function recovery in C₅ spinal cord injury mice. Methods Forty adult C57/BL mice were randomly divided into PTEN/SOCS3 group (injected PTEN virus and SOCS3 virus), PTEN group (injected PTEN virus), SOCS3 group (injected SOCS3 virus) and control group (injected empty control virus), 10 mice in each group. Adeno-associated-virus (AAV) were injected into the sensorimotor cortex. The activation of AKT/mTOR and JAK/STAT pathways in pyramidal neurons was detected by measuring the expression of p-S6 and p-STAT3 using immunofluorescence staining. Two weeks after injection, all the mice received C₅ crush injury. Biotinylated dextran amine (BDA) tracer was used to label corticospinal tract. The horizontal ladder and cylinder rearing tests were used to assess motor function recovery at pre-injury, and one week, two weeks, four weeks and six weeks after injury. Results Immunofluorescence staining results showed that AAV successfully infected the sensorimotor cortex pyramidal neurons.The expression of p-S6 in PTEN/SOCS3 group and PTEN group were significantly increased, the fluorescence intensity of p-S6[(25.429±2.991) AU and (26.171±2.140) AU] were significantly higher than SOCS3 group and control group [(9.544±2.474) AU and (9.558±1.650) AU] (P<0.001). The expression of p-STAT3 in PTEN/SOCS3 group and SOCS3 group were obviously increased, compared with PTEN group and control group [(12.952±1.282) AU and (14.394±1.983) AU], the fluorescence intensity of p-STAT3 in PTEN/SOCS3 group and SOCS3 group [(48.900±6.310) AU and (46.721±5.169) AU] were significantly higher (P<0.001). Compared with control group, the other three groups showed obvious axon regeneration after corticospinal tract injury. The regeneration distance and number were longer and more in PTEN/SOCS3 group (P<0.05). There was no significant difference between four groups in horizontal ladder and cylinder rearing tests at various time points (P>0.05). Conclusion Co-activation of AKT/mTOR and JAK/STAT pathways could improve neurons intrinsic regenerative growth capacity and successfully promote axon regeneration in adult spinal cord injury mice, but could not have better early motor function recovery.