Objective To observe the specific changes of content of cyclic guanosine monophosphate (cGMP) around meridian skin and specific influences of electroacupunture Neiguan (PC6) on cGMP of rats with acute myocardial ischemia (AMI). Methods With 6 male Wistar rats as normal group, 18 rats were made AMI model and divided into model group, high-frequency group and low-frequency group (n=6). The high-frequency and low-frequency group were given electroacupuncture in bilateral PC6 with 100 and 2 Hz for 20 min respectively. The content of cGMP in skin around PC6, Ximen (PC4), Tianquan (PC2), Waiguan (TE5) and Zusanli (ST36) was detected by using enzyme-linked immunosorbent method after treatment. Results In model group, cGMP content increased significantly around PC6, PC2, TE5 and ST36 compared with normal group (P <0.05,P <0.001). After the treatment with high-frequency or low-frequency electroacupunture in PC6, cGMP content decreased significantly in skin around PC6, PC2, TE5 and ST36 compared with model group (P <0.05, P <0.001). Conclusion High-frequency electroacupunture or high-frequency electroacupunture used in PC6 can protect rats from the injury of AMI. The mechanism may be related to the decrease of cGMP content around the acupoint areas in heart-related meridian.