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Jiehan Zhang,1,2 Hongrong Li,3,4 Dandong Wang,1,2 Jiaojiao Gu,2,5 Yunlong Hou,1,2 Yiling Wu1,2 1Hebei Medical University, Shijiazhuang, People’s Republic of China; 2National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China; 3Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, People’s Republic of China; 4Hebei Yiling Hospital, Shijiazhuang, People’s Republic of China; 5Hebei University of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yiling Wu; Yunlong Hou, Hebei Medical University, Shijiazhuang, People’s Republic of China, Email professorylw@163.com; houyunlonghrb@hotmail.comPurpose: The aim of our study was to investigate the mechanism by which the Chinese compound Shensong Yangxin Capsule (SSYX) reduces susceptibility to arrhythmia in db/db mice.Methods: The db/db mice without drug treatment served as the model group. Other-treated db/db mice were administered SSYX for 8 weeks. Electrocardiogram (ECG), electrical mapping, pathological changes, immunofluorescence staining, real-time quantitative PCR, and Western blot analyses were then conducted.Results: SSYX decreased arrhythmia susceptibility and shortened the abnormal ECG parameters of db/db mice. Meanwhile, SSYX restored irregular conduction direction and shortened the conduction time of the isolated heart. HE and Masson staining showed that SSYX alleviated inflammatory infiltration and collagen fiber deposition. Western blot showed that SSYX decreased the protein expression of ICAM-1, VCAM-1, and MCP-1 and increased the protein expression of occludin, ZO-1, eNOS, and Cx43. SSYX also increased the content of NO, decreased ET-1, TNF-α, IL-1β, IL-6, MCP-1, and CCR-2 mRNA expression, and increased Kv 4.2, Kv 4.3, Cav 1.2, and Nav 1.5 mRNA expression. Furthermore, SSYX decreased the fluorescence intensity of F4/80 and iNOS, increased the f