Objectives: The acupuncture has been used in the therapy of Alzheimer disease (AD), however, its neural underpins are still unclear. The aim of this study is to examine the acupuncture effect on the default mode network (DMN) in AD by using resting state functional magnetic resonance imaging (RS-fMRI). Methods: Twenty-eight subjects (14 AD and 14 normal controls (NC)) participated in this study. RS-fMRI data were acquired before and after acupuncture, while during the acupuncture, the procession of acupuncture stimulation on the acupoints of Tai chong (Liv3) and Hegu (LI4) lasted for 3 minutes. Results: Region of interest analysis showed that the impaired DMN connectivity in AD (identified by comparing the pre-acupuncture RS-fMRI of AD and NC), specifically the left cingulate gyrus (CG) and right inferior parietal lobule (IPL), were significantly changed for the better. The whole-brain exploratory analysis further demonstrated these results and found some new regions respond to the acupuncture effect on AD, with a cluster in the left posterior cingulate cortex (PCC), the right middle temporal gyrus (MTG) together with right IPL showed increased within-DMN connectivity; and the bilateral CG and left PCu showed decreased within-DMN connectivity. Moreover, the acupuncture effect on the right MTG was significantly correlated with disease severity as measured by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Conclusion: It was found that the acupuncture stimulation could modulate the DMN activity in AD. The current findings suggest that the acupuncture treatment on the relative earlier AD patients might have a better therapy effect.