Mental fatigue is a subjective fatigue state caused by long-term brain activity, which is the core of health problems among brainworkers. However, its influence on the process of brain information transmission integration is not clear. In this paper, phase amplitude coupling (PAC) between theta and gamma rhythm was used to study the electroencephalogram (EEG) data recorded before and after mental fatigue, so as to explain the effect of mental fatigue on brain information transmission mechanism. The experiment used a 4-hour professional English reading to induce brain fatigue. EEG signals of 14 male undergraduate volunteers before and after mental fatigue were recorded by Neuroscan EEG system. Phase amplitude coupling value was calculated and analyzed. t test was used to compare the results between two states. The results showed that theta phase of more than 90% of the electrodes in the whole brain area jointly modulated gamma amplitude of the right central area and the right parietal area, and the coupling effect among different brain regions significantly decreased (P < 0.05) when participants had felt mental fatigue. This paper shows that phase amplitude coupling can explain the influence of mental fatigue on information transmission mechanism. It could be an important indicator for mental fatigue detection. On the other hand, the results also provide a new measure to evaluate the effect of neuromodulation in relieving mental fatigue.