〔Abstract〕 Objective To explore the correlation between high density lipoprotein level and inflammatory reaction and renal function in patients with diabetic nephropathy. Methods 40 patients with diabetic nephropathy admitted to the Affiliated Hospital of Guangdong Medical University from January 2021 to August 2022 were selected as an observation group, and 40 patients with simple diabetes but excluding renal lesions during the same period were selected as a control group. The levels of blood lipids, blood glucose, renal function indicators and inflammatory factors in the two groups were compared, and the correlation between highdensity lipoprotein and inflammatory factors and renal function indicators in the two groups was analyzed respectively. Results The levels of total cholesterol, triglyceride, low density lipoprotein, fasting 8 h blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, urea nitrogen and creatinine in the observation group were higher than those in the control group, but the levels of high density lipoprotein were lower than those in the control group, with statistical significance (P < 0.05). The levels of interleukin-1, interleukin-6, C-reactive protein and tumor necrosis factor-α in the observation group were higher than those in the control group, with statistically significant (P < 0.05). There was no correlation between high density lipoprotein and inflammatory factors or renal function in the control group. The levels of high density lipoprotein in the observation group were negatively correlated with interleukin-1, interleukin-6, C-reactive protein and tumor necrosis factor-α, urea nitrogen, creatinine. Conclusion In diabetic nephropathy patients, the level of high density lipoprotein decreased significantly, and the inflammatory reaction and renal injury were obvious. The levels of high density lipoprotein were negatively correlated with the levels of inflammatory factors and renal injury indicators.