Abstract: OBJECTIVE To explore the effects of Tongxinluo capsule on p38 mitogen-activated protein kinase (p38 MAPK) inflammatory signal pathway in mice with diabetic cardiomyopathy. METHODS Forty KK/Upj-Ay mice were randomly divided into model group and Tongxinluo(low, middle, high) groups(n=10, respectively). C57BL/6 mice were selected as control group(n=10). After 12 weeks, the mice were sacrificed and were weighed. The fasting blood-glucose(FBG), glycosylated hemoglobin(HbA1c), triglyceride(TG), total cholesterol(TC) and left ventricular index were measured. Radioimmunoassay was used to measure the contents of serum tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6). The pathological changes in the myocardium of mice were observed by HE staining. The expression levels of total p38 MAPK, phosphorylated p38 MAPK(p-p38 MAPK), total c-Jun N-terminal kinase(JNK), phosphorylated JNK(p-JNK), total extracellular-signa1 regulated kinase(ERK), phosphorylated ERK(p-ERK) were detected by Western blot. RESULTS Compared with the control group, the level of FBG, HbA1c TG, TC, TNF-α and IL-6, left ventricular weight index, and the expression of p-p38 MAPK, p-JNK, p-ERK in the model group were higher. Tongxinluo capsule reduced myocardium pathological damage and the level of TG, TC, TNF-α and IL-6, and down-regulated the expression of p-p38 MAPK in myocardium of diabetic mice, but had no effects on body weight, FBG, HbA1c and the expression of p-JNK, p-ERK. The total expression of p38 MAPK, JNK and ERK proteins among four groups had no significant difference. CONCLUSION Tongxinluo capsule can ameliorate the myocardium damage and improve the function of diabetic myocardium by down-regulating the phosphorylation of p38 MAPK and inhibiting the inflammation reaction.