ObjectiveTo investigate the effect of gross saponins of Tribulus terrestris (GSTT) on erectile function in rats resulting from type 2 diabetes mellitus (T2DMED).MethodsThe T2DMED model was constructed by high-fat and high-sugar feeding and streptozotocin injection. After 4 weeks of GSTT intervention. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured in each group. The level of nitric oxide (NO) in the cavernous tissue was detected using the nitrate reductase method. The production of reactive oxygen species (ROS) was detected using DHE fluorescent probe detection. Cyclic adenosine monophosphate (cGMP) level was detected by enzyme-linked immunosorbent assay, and endothelial nitric oxide synthase (eNOS) was detected using immunohistochemistry. Masson staining was used to detect the cavernosal smooth muscle/collagen ratio. Apoptosis in endothelial cells was measured using TUNEL. Western blotting method to detect the protein expression level of eNOS, TIMP-1, cleaved caspase 3, and cleaved caspase 9.ResultsAfter treatment, the ICP and ICP/MAP values of the GSTT were significantly higher than those of the T2DMED group (P<0.05). Unlike the T2DMED group, the GSTT group showed significantly increased NO levels (P<0.05) and decreased ROS levels (P<0.05). There was no significant difference between the GSTT group and the sildenafil group in increasing cGMP levels (P>0.05), and the mixed group had higher levels than these two groups (P<0.05). Immunohistochemistry and Western blotting showed that the expression of eNOS in the GSTT was significantly higher than that in the T2DMED groups (P<0.05). Masson staining showed that the smooth muscle/collagen ratio of the GSTT group was significantly higher than that of the T2DMED groups (P<0.05), the expression of TIMP-1 was lower than that of T2DMED group (P<0.05). TUNEL assay showed that the apoptotic index and cleaved caspase 3 and cleaved caspase 9 expression level of GSTT group were lower than that of the T2DMED group (P<0.05).ConclusionGSTT can protect T2DMED rats’ erectile function by improving penile endothelial function and inhibiting cavernosum fibrosis, inhibiting apoptosis, and is synergistic with sildenafil.