Knowing how the brain processes Chinese characters of different frequencies of occurrence may shed light on the extent to which orthographic variations of different languages can influence reading processes in the brain. In the present study, event-related fMRI was used to investigate frequency effects on Chinese character processing. Reading low-frequency characters invoked higher activation in several brain regions including the left premotor/inferior frontal gyrus, supplementary motor area, left anterior insula, left posterior inferior temporal gyrus, left superior parietal cortex, and lingual cortex, while reading high-frequency characters resulted in higher activation in the left supramarginal/angular gyrus and left precuneus. The activation pattern of reading infrequently encountered characters reflects a more demanding processing procedure of retrieving, formulating, and coordinating the phonological output. Access to the lexical route may benefit the reading of high-frequency characters. By uncovering the differential brain responses in reading Chinese characters of different occurrence frequencies, not only has a substantial overlap between functional neuroanatomy of reading Chinese and alphabetical languages been demonstrated, but also features permitting the separation of language-specific content from universal mechanisms.