Objective To observe the effects of different Mongolian acupuncture methods on neurons form in frontal lobe and NO-cGMP signaling pathways in rats with chronic stress depression; To explore biological mechanism of different Mongolian acupuncture methods for depression.Methods The male SD rats were randomly divided into control group, model group, fluoxetine group, Mongolian silver acupuncture group, Mongolian acupuncture three modulation methods group, and the combination of acupuncture with fluoxetine group (8 rats in each group). Except for control group, other rats were kept alone. Rats receive different treatment 1 hour before stimulations. Behavior changes were observed after 28 days. Hippocampus and frontal lobe tissues were collected. Frontal lobe neurons form changes were observed through different dyeing methods. The content of NO-cGMP was detected by radioimmunoassay and nitrate reductase method.Results Results of Nissl's staining showed that the neuronal pyramidal cells in the frontal lobe of model group rats arranged disorderedly, morphology was not intact and the number was obviously reduced. Nissl's staining got shallow and the most were blurry. The form of the frontal lobe neurons in Mongolian acupuncture three modulation methods group and Mongolian acupuncture group were good, Nissl's staining was dark blue. HE staining results showed that cytomembrane of frontal lobe neurons in model group rats ruptured, and structure was not clear. some cells fell off and formed into cavities. In Mongolian acupuncture three modulation methods group and Mongolian silver acupuncture group, the frontal lobe cells arranged regularly, cellular level was rich, and the nerve cell membrane was complete. The content of NO-cGMP in frontal lobe and hippocampus tissues was significantly elevated in model group. Mongolian acupuncture, Mongolian acupuncture three modulation methods, fluoxetine, and the combination of acupuncture with fluoxetine treatments all could reverse the changes.Conclusion Different Mongolian acupuncture methods may treat depression through regulating and controlling the expression of NO-cGMP.