Objective To investigate the relationship of epicardial adipose tissue volume (EATV), urinary microalbumin/creatinine ratio (UACR) and serum levels of inflammatory factors, including lipoprotein-associated phospholipase A2 (Lp-PLA2), fractalkine (FKN), tumor necrosis factor-α (TNF-α), matrix metaloproteinase-9 (MMP-9), insulin-like growth factor-1 (IGF-1), and cystatin C (Cys C), with severity of coronary lesions in coronary heart disease (CHD) patients. Methods A total of 130 patients with freshly-diagnosed coronary artery stenosis in our department from March 2016 to August 2017 were recruited in this study. Another 32 non-CHD patients without such stenosis served as control group. The patients with coronary artery stenosis were identified by coronary angiography, and through synergy between percutaneous coronary intervention (PCI) with TAXUS stent and cardiac surgery (SYNTAX), their SYNTAX scores were calculated. According to the score, the patients were assigned into low (≤22), moderate (23-32) and high score (≥33) groups. EATV was calculated based on coronary artery spiral CT images. Latex agglutination turbidimetric immunoassay and enzyme-linked immunosorbent assay were used to determine UACR and inflammatory factor levels. The relationship of EATV, UACR and serum levels of inflammatory factors with severity of coronary lesions were analyzed in 4 groups of patients. SPSS statistics 17.0 was used to perform the statistical analysis. Student′s t test, Chi-square test, or Fisher exact test was employed for comparison between groups based on different data types. Pearson product-moment correlation analysis was adopted for the correlation analysis, and logistic stepwise regression analysis for multiple factor analysis. Results The EATV, Lp-PLA2, FKN, MMP-9, Cys C levels and UACR were obviously higher in the high score group than the moderate and low score groups and control group (P<0.05). The high score group also had higher IGF-1 than the control and moderate score group and higher TNF-α than the control and low score group (both P<0.05). The moderate score group had significantly higher EATV, Lp-PLA2, MMP-9 and TNF-α levels and UACR than the control and low score group, lower IGF-1 than the low score group, but higher FKN and Cys C levels than the control group (P<0.05). While, the EATV and IGF-1 levels were notably higher in the low score group than control group (P<0.05). Correlation analysis showed that SYNTAX score was positively correlated with EATV (r=0.41), UACR (r=0.69), Lp-PLA2 (r=0.72), IGF-1 (r=0.25), FKN (r=0.52), TNF-α (r=0.49), MMP-9 (r=0.67) and Cys C (r=0.15). Logistic stepwise regression analysis indicated that IGF-1 (OR=1.064,5%CI 1.024-1.106, P=0.002), MMP-9 (OR=1.049,5%CI 1.018-1.080, P=0.002), Cys C (OR=797.355,5%CI 33.729-999.999, P=0.001) and EATV (OR=1.042,5%CI 1.018-1.067, P=0.005) were risk factors for CHD. Conclusion Larger EATV, higher UACR and higher serum levels of inflammatory factors (Lp-PLA2, IGF-1, FKN, TNF-α, MMP-9 and Cys C) indicate high score of SYNTAX and severe coronary lesions. IGF-1, MMP-9, Cys C and EATV might be risk factors for CHD.