Sertraline is a commonly used antidepressant of inhibiting selective serotonin reuptake. To Induce kinetic model of Sertraline, we imaged C11 Sertraline radio-labeled tracer in human brain at PET scanner. To explore the input function of the pharmacological kinetic model, we measured the real time blood samples from each PET scanning person for equilibrium constants and metabolism fraction. Dynamic C-11 Sertraline Brain PET scans were acquired during 90 min (n=3) or 120 min (n=2) in 5 healthy males (average age 32.4 y, range 21–43 y). We construct kinetic models for C-11 Sertraline in putamen, caudate in human brain combining each person's 3D 1 SPGR MRI scans. Region of Interest was drawn to 7 regions to derive tissue time–activity curve. Three-Compartment models with irreversible (k4=0, 3C3P) and reversible (3C4P), Two-compartment models with reversible (2C2P) was considered as the test model. To select the best fitting model, Akaike information criterion and F-test was done as the statistical method. In the blood sample, metabolited radio-labeled material fraction was neglegible. The obtained time–activity curve of C-11 Sertraline at the brain showed that its binding potential is very high and slow clearance property was seen in all the regions in the brain. For the calibration, we did phantom experiment in PET scanners and gamma counter. As the statistical evaluating standard, both Akaike information Criterion test and F test which showed that 2C2P was the most fitting kinetic model for C-11 sertraline in human brain were done. Average values of K1 (ml/min/g) and k2 (1/min) estimated using this model were 0.54 and 0.012 in putamen and 0.43 and 0.016 in cerebellum. As the time–activity curve at the brain region was saturated to the equilibrium state, C-11 Sertraline would bind to the target region almost irreversibly and yield high distribution volume. The 2-Compartment model is suitable kinetic model by this C-11 sertraline analysis. This kinetic model will be helpful for studying dynamic kinetic modeling for antidepressed patient.