In order to study the effects of microwave (MW) exposure on the mitochondrial transcription factor A(Tfam) expression in neurons and explore the relationship between Tfam and the energy metabolism disturbance the experiment model with exposing primary cultured cortical neurons to the microwave for 15min has been established in our group. The concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) at 0h, 6h, 12h, 24h and 48h after exposure has been measured by high performance liquid chromatography (HPLC). And the real-time polymerase chain reaction (PCR) and fluorescence western-blot has been applied to detect the changes of the Tfam messenger ribonucleic acid (mRNA) and protein levels respectively. The results show that the concentration of ATP decreases in a time-dependent manner after exposure and both of the mRNA and protein expression of Tfam are up-regulated. It demonstrates that microwave exposure dramatically disturbs energy metabolism of neurons. However, newly-increased Tfam can’t up-regulate the ATP concentration as expected. It suggests microwave may have an adverse effect on the biological activity of Tfam in regulating the energy metabolism through inhibiting the import of Tfam from cytoplasm into mitochondria.