Previous studies have suggested the potential efficacy of middle chain fatty acids (MCFAs) in the treatment of mood disorders and cognitive dysfunction. MCFAs are metabolized to ketone bodies in astrocytes; however, their effects on neuronal development including neurotrophic factor level are not well-understood. In the present study, we examined the effect of MCFAs on the mRNA expression of growth factors and cytokines in primary cultures of cortical astrocytes. The effect of MCFAs on neuron-astrocyte interaction in neuronal maturation was also determined using co-culture and astrocyte-conditioned medium. Lauric acid (LA) typically increased the mRNA expression of glial-derived neurotrophic factor (), interleukin-6 (), and C-C motif chemokine 2 () in astrocytes. LA-induced phosphorylation of extracellular signal-regulated kinase contributed to these changes. In primary cultures of cortical neurons containing astrocytes, LA enhanced the presynaptic protein levels. Astrocyte-conditioned medium after LA treatment also enhanced the presynaptic protein levels in the cortical neuron cultures. These results suggest that LA increase the mRNA expression of GDNF and cytokines in astrocytes, and thereby, enhances the presynaptic maturation.