The aim of this study was to investigate the autonomic responses and central manifestations by peripheral FIR stimulation. Ten subjects (mean ± SD age 26.2 ± 3.52 years) received FIR stimulation at left median nerve territory for 40 min. Electrocardiograph was continuously recorded and heart rate variability (HRV) were analyzed. By using a 3 T-MRI scanner, three sessions of resting-state functional magnetic resonance images (fMRI) were acquired, namely, before (baseline-FIR), immediately after (IA-FIR) and 15 min after FIR was turned off (Post-FIR). The fractional amplitude of low-frequency (0.01-0.08 Hz) fluctuation (fALFF) of each session to evaluate the intensity of resting-brain activity in each session was analyzed. Our results showed that FIR stimulation induced significant HRV responses such as an increasing trend of nLF and LF/HF ratio, while FIR increased fALFF in right superior front gyrus, middle frontal gyrus and decreased the resting brain activity at fusiform gyrus, extrastriae cortex, inferior temporal gyrus and middle temporal gyrus, especially 15 min after FIR was turned off. We conclude that the central manifestation and the autonomic responses are prominent during and after FIR stimulation, which provide important mechanistic explanation on human disorder treated by such energy medicine.