To compare the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints (Biao indicates pathogenic factors of disease, Ben refers to body constitution) on a rat model of irritable bowel syndrome with diarrhea (IBS-D). Forty female SD rats were randomly divided into 4 groups:normal group, model group, moxibustion group, and acupuncture group, with 10 rats in each group. The IBS-D rat model was established by administering acute-chronic stress combined with folium sennae gavage for 28 days. Rats in the moxibustion group received moxibustion at bilateral "Zusanli"(ST36), "Guanyuan"(CV4), and "Neiguan"(PC6), while those in the acupuncture group received acupuncture at the same acupoints, both for 15 min every time, once a day. The treatments were administered for 21 days. The loose stool rate was observed. Colonic pain threshold and colonic distension threshold were measured by a self-made balloon catheter. Total distance traveled and grid crossing numbers were observed by open field test. Heart rate variability(HRV) time domain indexes SDANN and PNN50 were acguired by using electrophysiological recorder. Histopathological changes in the colon tissue were observed after HE staining. Contents of interleukin-6(IL-6), IL-8, and tumor necrosis factor-alpha(TNF-α) in serum were detected by ELISA. Compared with the normal group, rats in the model group showed increased loose stool rate(P<0.05), decreased pain threshold and distension threshold(P<0.05), reduced total distance traveled and grid crossing numbers in the open field test(P<0.05), decreased HRV time domain indexes SDANN and PNN50(P<0.01, P<0.05), and elevated levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the model group, the moxibustion group and acupuncture group showed decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50 (P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the acupuncture group, the moxibustion group showed further decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50(P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). No significant pathological changes were observed in the colon tissue of rats in each group. Moxibustion of combined "Biao-Ben" acupoints is more effective in regulating HRV and serum IL-6, IL-8, and TNF-α contents in the IBS-D rat model. Based on the combined "Biao-Ben" acupoints method, moxibustion has better therapeutic effects on IBS-D than acupuncture.