Objective To examine the effect of modified ectopic pregnancy formula II on levels of apoptosis- related proteins Caspase-7, Caspase-9, and Caspase-3 in the endoplasmic reticulum stress Caspase-12 signaling pathway in human trophoblasts, as well as associated changes in cell ultrastructure, to explore its treatment mechanism for ectopic pregnancy. Methods SD rats were divided into a negative control group ( group B), low-, medium-, and high-dose Chinese medicine groups ( groups C, D, E), a methotrexate group ( group F), and a combined Chinese and Western medicine group ( group G). After receiving the corresponding drug treatment, we collected blood to prepare a drug- containing serum. The drug-containing serum from each group was applied to HTR-8/ SVneo for 24 h, and cells not treated with drug-containing serum were set as a blank control group (group A). The expression levels of apoptotic genes Caspase- 7, Caspase-9, Caspase-3 protein and mRNA in HTR-8/ SVneo cells were detected via Western blot and real-time quantitative PCR. Transmission electron microscopy was used to observe changes in cell ultrastructure. Results (1) There was no difference between group A and group B in terms of Caspase-7, Caspase-9, or Caspase-3 protein levels and relative mRNA expression (P> 0. 05). Compared with group B, expression levels of Caspase-7 mRNA, Caspase-9 protein, and Caspase-3 protein and mRNA were significantly up-regulated in group C ( P < 0. 05), but we found no differences in Caspase-7 protein or Caspase-9 mRNA expression (P> 0. 05). In terms of Caspase-7, Caspase-9, and Caspase-3 protein and mRNA expression, expression was significantly increased in groups D, E, F, and G compared with group B (P < 0. 05), and expression in Group E was significantly up-regulated compared with group D ( P < 0. 05). Group E was compared with group F, expression levels of Caspase-7, Caspase-9 protein and mRNA, and Caspase-3 protein were significantly up-regulated (P < 0. 05). Group E was compared with group G, expression of Caspase-9 protein and mRNA and Caspase-3 protein was significantly increased (P <0. 05). There was no difference between group F and group G (P> 0. 05). ( 2) Transmission electron microscopy indicated that the cell chromatin in group A and group B was evenly distributed in the nuclear membrane, and the endoplasmic reticulum, mitochondria, and Golgi apparatus were clearly visible. Compared with group B, the cell microvilli in groups C, D, E, F, and G were reduced, chromatin was condensed, heterochromatin was marginalized, some mitochondria were swollen, disordered, broken, or even absent, and mitochondrial vacuolation were typical apoptotic characteristics. Conclusions Modified ectopic pregnancy formula II may activate the Caspase-12 signaling pathway of endoplasmic reticulum stress, destroy the morphological structure of trophoblasts, up-regulate the expression of Caspase-7, Caspase-9, and Caspase-3 apoptosis-related genes, and promote trophoblast apoptosis.