An important component in the pathogenesis of neurodegeneration is chronic neuroinflammation. This complex entity is established when resolution processes fail to limit pro-inflammatory stimuli, and it is an important triggering factor for neuronal death. The inflammation/resolution balance is governed by the activation of G protein-coupled receptors (GPCR) by specific ligands. In the central nervous system, these mechanisms have been poorly described, since GPCR ligands responsible for triggering resolution responses are negligible and elusive lipid compounds. Thus, we aimed to investigate whether resolution mechanisms operated as an early response in neurons and astrocytes to overcome pesticide-induced neurotoxicity. We found that astrocytes rescued neurons from pesticide-induced death. Using the endogenous FPR2/ALX agonist, lipoxin A4, and its antagonist, Quin-c7, we demonstrated the involvement of this GPCR receptor and its lipid ligand as responsible for astrocyte-induced neuroprotection. In addition, pesticide-exposed neurons were able to promote a proliferative A2 phenotype in astrocytes, a process that was also dependent on FPR2/ALX activation. These results revealed that neuronal fate upon pesticide-induced toxicity relies on resolution mechanisms triggered by lipoxin A4.