The maintenance of a dynamic balance between excitatory and inhibitory synapses in the neocortex is critical for brain function. Many psychiatric disorders are characterized by disturbance of E/I balance. In this study we examined the potential of the fMRI time-series complexity metric multi-scale entropy (MSE) to act as a biomarker for E/I balance, using a non-human primate (NHP) model. We disturbed the E/I balance with the sub-anesthetic ketamine, which induces disinhibition of projection neurons, especially in prefrontal cortex (PFC) during fMRI of conscious NHPs. Our results confirmed that fMRI MSE is a sensitive marker for E/I balance in the brain.