Introduction: By aging population, the heart failure and its life-threatening complications have become an enormous issue in public health. Regarding the inflammation as a major contributing pathological factor, the determination of most important inflammatory targets for immunomodulation is a problematic puzzle in the treatment of heart failure patients and the inflammatory pathways primarily involved in different underlying conditions contributing to heart failure can be an area which is worthy of focused research. Considering the dilated cardiomyopathy (DCM) as a relatively high-incident disease leading to heart failure, the aim of this study is to determine the difference in the expression level of interleukin (IL)-6 and IL-18 in patients with ischemic and idiopathic DCM. Methods: 39 non-diabetic patients with ischemic and 37 ones with idiopathic DCM were enrolled in the study. 48 healthy individuals were also considered as control group. For quantitative determination of the mRNA expression level of IL-6 and IL-18 genes, an in-house- SYBR Green real-time PCR was used and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was considered as internal control gene. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) was calculated by 2D echocardiographic assessment. Data were finally analyzed via SPSS statistical software version 19.0 using independent t test and 2-∆∆Ct method and P<0.05 were considered statistically significant. Results: The IL-6 was significantly higher expressed in patients with ischemic and idiopathic DCM than in healthy controls (274.3 and 168.8 times, respectively, both P values <0.001). The same higher expression of IL-18 was observed in ischemic DCM (48.5 times) and idiopathic DCM (45.2 times) compared with healthy individuals (both P values <0.001). Conclusion: Both ischemic and idiopathic DCM associates with IL-6 and IL-18 overexpression. However, no significant difference was observed between these two subtypes of DCM in either interleukin expression level. There is certainly need to further studies for evaluating the uniformity of results and also assessing other molecules in determining their roles in pathophysiology and probable utility for management.