Significance Damage to axons in the CNS typically results in permanent functional deficits. Boosting intrinsic programs such as mammalian target of rapamycin (mTOR) signaling can dramatically augment the axon regenerative capacity of injured neurons. Because certain types of neurons respond to axotomy by maintaining their mTOR activation, we hypothesized that it might be helpful to use this property to promote axon regeneration. We found that the light-responsive G protein-coupled receptor (GPCR) melanopsin could promote axonal regeneration after optic nerve crush by activating mTOR. We also showed that light, Gq/11 signaling, and neuronal activity contribute to the mechanism that underlies this effect. Activating Gq signaling through a chemogenetic approach promoted axon regeneration. Thus, we provided evidence for modulating neuronal activity through GPCR signaling in regulating intrinsic axon growth capacity.