A study area in Jilin was selected from lots of arsenic endemic regions, which are mainly distributed in Taiwan, Xinjiang, Inner Mongolia, Shanxi and Jilin. A total of 196 groundwater samples were collected, which not only covered the whole study area but also extended to different depths/aquifers that included Quaternary phreatic groundwater, Quaternary Baitushan Formation confined groundwater and Neogene confined groundwater. The result reveals that the distribution of arsenic at the present time has a close relationship with the spatial variation of Fe, Mn as well as Cl-, PO34- , HCO3-, SO24- and Se. An inverse geochemical model was established to demonstrate the above relationship by using the PHREEQC software. The simulation results have confirmed that the arsenic presence and its distribution in the groundwater of this area result largely from the leaching - migration-accumulation from the edge to the central area of the basin.