Ammonia induces astrocyte swelling, which is strongly associated with overexpression of aquaporin-4. However, the mechanisms by which ammonia induces astrocyte swelling, and subsequently upregulating aquaporin-4 expression, remain unknown. In the present study, astrocytes were cultured in vitro and exposed to ammonium chloride (NH4Cl), followed by propofol, protein kinase C agonist, or antagonist, respectively. Astrocyte morphology was observed by light microscopy, and aquaporin-4 expression was detected by western blot analysis. Results showed that propofol or protein kinase C agonist significantly attenuated the degree of NH4Cl-induced astrocyte swelling and inhibited increased aquaporin-4 expression. Propofol treatment inhibited aquaporin-4 overexpression in cultured astrocyte induced by NH4Cl; protein kinase C pathway activation is potentially involved. Ammonia induces astrocyte swelling, which is strongly associated with overexpression of aquaporin-4. However, the mechanisms by which ammonia induces astrocyte swelling, and subsequently upregulating aquaporin-4 expression, remain unknown. In the present study, astrocytes were cultured in vitro and exposed to ammonium chloride (NH4Cl), followed by propofol, protein kinase C agonist, or antagonist, respectively. Astrocyte morphology was observed by light microscopy, and aquaporin-4 expression was detected by western blot analysis. Results showed that propofol or protein kinase C agonist significantly attenuated the degree of NH4Cl-induced astrocyte swelling and decreased increased aquaporin-4 expression. Propofol treatment inhibited aquaporin-4 overexpression in cultured astrocyte induced by NH4Cl; protein kinase C pathway activation is potentially involved.