【】 Objective To investigate the mechanism by which Yangmai Tongluo Formula improves microcirculation disorders induced by high homocysteine (Hcy) through the regulation of acid sphingomyelinase (ASM) and endoplasmic reticulum stress (ER stress) pathways. Methods Fifty male C57/6J mice were randomly divided into a control group, an Hcy model group, low/high-dose Yangmai Tongluo Formula groups (5.3, 10.4 g/kg), and a folic acid group [1](0.08 g/kg). Except for the control group, the other mice were induced with a microcirculation disorder model by drinking water containing 1.8 g/L Hcy for 6 weeks. After 2 weeks of modeling, the mice were administered the corresponding treatments by gavage for 4 weeks. Serum Hcy concentration and blood perfusion volume of the lower extremity microvessels were measured, and the expression of ZO-1, ZO-2, ICAM-1, VCAM-1, ASM, GRP78, and CHOP proteins in the cardiac microvascular endothelium was analyzed using immunofluorescence. Results Compared with the control group, Serum Hcy levels were significantly increased in the Hcy model group (P < 0.05). Although, Compared to the Hcy model group, Yangmai Tongluo Formula did not significantly reduce Hcy levels, the high-dose group significantly increased blood perfusion in the lower extremities (P < 0.01) and restored the expression of ZO-1 and ZO-2 in the cardiac microvascular endothelium (P < 0.001). Additionally, it inhibited the expression of ICAM-1, VCAM-1, ASM, GRP78, and CHOP (P < 0.05), with effects comparable to those of the folic acid group. Conclusions Yangmai Tongluo Formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress. Its mechanism is closely related to the regulation of endothelial inflammation and barrier stability, providing experimental evidence for the treatment of microvascular diseases with traditional Chinese medicine.