BACKGROUND: In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects' psychological attitude to acupuncture and their physical state are the three most confounding factors. OBJECTIVE: To obtain more precise and accurate cerebral fMRI mapping of acupuncture. DESIGN AND SETTING: A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China. PARTICIPANTS: Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D. INTERVENTIONS: Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI. RESULTS: Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas. CONCLUSIONS: The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results.