Objective The aim of this study was to explore the mechanism of Yiqi Huoxue recipe in regulating immune inflammatory response in rats with coronary heart disease syndrome of qi deficiency and blood stasis. Methods Thirty SD rats were randomly divided into control group, model group, and recipe group. The model of qi deficiency and blood stasis syndrome of coronary heart disease was prepared by exhaustion, food control, and ligation of the left anterior descending branch of the coronary artery in model group, and recipe group. recipe group was pretreated with Yiqi Huoxue Recipe for 14 days from day 8 of modeling. On day 25, serum, heart, spleen, and aorta were collected for cytokine quantification and histopathological examination. Results (1)Serum levels of IL-37 and IL-35 were significantly lower in model group, than control group ( P< 0. 00001 ). ( 2 ) After treatment, the serum levels of IL-37 and IL-35 were significantly higher in recipe group than model group(P< 0. 00001). HE staining showed a large degree of inflammatory cell infiltration in the myocardial stroma in model group. The red pulp area of spleen tissue was smaller, and a large number of lymph nodes between marginal zone ( MZ) and the periarterial lymph sheath were seen in white pulp. Hyperplasia, structural disorder, the presence of foam cells, and lipid deposition were seen in the aortic intima in model group. Inflammatory cell infiltration of myocardial tissue was significantly lower in recipe group than in the model group. The intima of the aorta was thin, and scars were seen at damaged fibers. A normal distribution of trabecula(T)and splenic sinus(SS) was seen in spleen tissue and central antery(CA) morphology was regular in recipe group. ( 3) The average optical densities and protein contents of IL-35 and IL-37 in the myocardium, aorta, and spleen of model group were significantly lower than those in control group(P< 0. 00001). The average optical densities and protein contents of IL-35 and IL-37 in the myocardium, aorta, and spleen of rats in recipe group were significantly higher than those in control group (P< 0. 00001). Conclusions CHD model rats with qi deficiency and blood stasis syndrome support the theory of simultaneous treatment of heart and spleen, Yiqi Huoxue recipe improves the inflammatory state of CHD with qi deficiency and blood stasis syndrome, and its mechanism is related to the upregulation of IL-35 and IL-37.