Functional magnetic resonance imaging (fMRI) was used to study the activated brain areas of human during simple and complex digital calculation, and to investigate the role of cortical and subcortical structures involved in the mental calculation. Sixteen right-handed healthy volunteers performed mental calculation of simple and complex addition/subtraction respectively, while the fMRI data were recorded by a Seimens 1.5 T MR machine. Block-design was used in the tasks. Two calculation tasks and one base-line tasks were performed for the block-design. Simple calculation task was single-digit addition and subtraction, while the complex was multi-digit addition and subtraction. The base-line task was to tell whether the two numbers were the same in every trial. Statistical parametric mapping (SPM99) was employed to process data and localize functional areas. We compared the average activation intensity of each activated brain regions in the same calculation task and the activation intensity of the same regions in both tasks respectively. Both the cortex and the subcortical structures including basal ganglia and thalamus were activated during simple and complex mental calculations. Similar brain regions in subjects including frontal lobe, parietal lobe, occipital lobe, cingulate gyrus, thalamus and cerebellum were engaged in simple and complex addition/subtraction. In the same task, activation intensity of all activated brain areas differed insignificantly. Compared with the complex task, the right parietal lobe was not activated in the simple one. The subcortical structures such as the caudate nucleus and the left marginal division of the striatum (MrD) were activated in both two calculation tasks. The cortical regions involved in both simple and complex addition/subtraction were similar. In conclusion, both the cortex and the subcortical structures were activated during the mental calculation. The cortex including the frontal cortex, parietal cortex, and cingulate gyrus were activated during mental calculation, while the subcortical structures such as the caudate nucleus, the globus pallidum and the left marginal division of the striatum also played a critical role in the neural networks of the calculation at the same time. Right parietal lobe (supramarginal gyrus) was engaged only in the complex task, which suggested that this region might be involved in the visuospatial memory and processing.