Objective To investigate the changes in serum levels of vaspin and nesfatin-1 and their relationship with levels of inflammatory factors in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) after liraglutide treatment.Methods The clinical data of 214 patients with DN admitted to the National Hospital of Guangxi Zhuang Autonomous Region from April 2020 to August 2022 were retrospectively analyzed. Among them, 105 patients receiving conventional treatment for DN were included in the control group and 109 patients receiving liraglutide combined with conventional treatment for DN were included in the study group. The therapeutic efficacy in both groups was observed after three months of treatment. The biomedical indicators including blood glucose, blood lipids and those related to renal function were compared between the two groups before and after treatment. The changes in serum levels of vaspin, nesfatin-1 and inflammatory factors before and after treatment were compared between the two groups. Pearson method was used to analyze the relationship between serum levels of vaspin and nesfatin-1 and those of inflammatory factors.Results The differences of the levels of fasting blood glucose, 2-hour postprandial glucose, and glycosylated hemoglobin, and those of insulin resistance index (HOMA-IR) and islet β-cell function index (HOMA-β) before and after treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) before and after treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) as well as the urinary albumin/creatinine ratio (UACR) before and after treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of vaspin and nesfatin-1 before and after treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) before and after treatment in the study group were higher than those in the control group (P < 0.05). Pearson correlation analysis demonstrated that the level of vaspin was negatively correlated with the levels of TNF-α, IL-6 and IL-1 in the study group before treatment (r = -0.745, -0.691 and -0.701, all P < 0.05) and after treatment (r = -0.761, -0.748 and -0.712, all P < 0.05). The level of nesfatin-1 was negatively correlated with the levels of TNF-α, IL-6 and IL-1 in the study group before treatment (r = -0.628, -0.712 and -0.683, P < 0.05) and after treatment (r = -0.803, -0.828 and -0.814, all P < 0.05). No adverse reactions occurred in either group during treatment.Conclusion Liraglutide treatment can significantly improve glucose and lipid metabolism, renal function, and serum levels of vaspin and nesfatin-1 in DN patients. Besides, it down-regulates the levels of inflammatory factors, and the serum levels of vaspin and nesfatin-1 are related to the levels of inflammatory factors before and after liraglutide treatment.