The intercellular communication within the central nervous system (CNS) is of great importance for in maintaining brain function, homeostasis, and CNS regulation. When the equilibrium of CNS is disrupted or injured, microglia are immediately activated and respond to CNS injury. Microglia-derived exosomes are capable of participating in intercellular communication within the CNS by transporting various bioactive substances, including nucleic acids, proteins, lipids, amino acids, and metabolites. Nevertheless, microglia activation is a double-edged sword. Activated microglia can coordinate the neural repair process and, conversely, can amplify tissue injury and impede CNS repair. This work reviewed the roles of exosomes derived from microglia stimulated by different environments (mainly lipopolysaccharide, interleukin-4, and other specific preconditioning) in CNS injury and their possible therapeutic potentials. This work focuses on the regulation of exosomes derived from microglia stimulated by different environments on nerve cells. Meanwhile, we summarized the molecular mechanisms by which the relevant exosomes exert regulatory effects. Exosomes, derived from microglia stimulated by different environments, regulate other nerve cells during the repair of CNS injury, having beneficial or detrimental effects on CNS repair. A comprehensive understanding of the molecular mechanisms underlying their role can provide a robust foundation for the clinical treatment of CNS injury.