Abstract: Objective To explore the correlation between serum micro RNA (miRNA) level and inflammatory factors in patients with early diabetic nephropathy. Methods A total of 68 diabetes patients admitted into Department of Endocrinology, Huai'an First Affiliated Hospital of Nanjing Medical University from January to December 2018 were selected in the current study. According to Mogensen stages, the patients were divided into two groups: a diabetes (DM) group (urinary albumin/creatinine <30 mg/g, n=32) and an early diabetic nephropathy (DN) group (30 mg/g≤urinary albumin/creatinine≤300 mg/g). Meanwhile, healthy volunteers who received physical examination in our hospital during the same period were enrolled into a control group (n=30). The levels of serum miRNA21 and miRNA155 in each group were detected by real-time quantitative PCR, and their correlation with high-mobility group box-1 (HMGB1), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) was analyzed. Results The DM and early DN groups produced remarkably decreased levels of miRNA21 and increased levels of miRNA155, compared with the control group (P＜0.05). For patients with early diabetic nephropathy, their miRNA21 levels were negatively correlated with the levels of HMGB1, TNF-α, and IL-6 (r=-0.809, P＜0.05; r=-0.841, P＜0.05; r=-0.851, P＜0.05), while their miRNA155 levels were positively correlated with HMGB1, TNF-α, and IL-6 (r=0.829, P＜0.05; r=0.851, P＜0.05; r=0.862, P＜0.05). Conclusions Serum miRNA21 can alleviate the progression of diabetic nephropathy, while miRNA155 is involved in the occurrence of early diabetic nephropathy, which may be related to regulation of the expression of inflammatory factors.