ObjectiveThis study applied Mendelian randomization to explore the potential causal relationship between inflammatory factors and diabetic nephropathy. MethodsSummary-level data from genome-wide association studies of inflammatory factors and diabetic nephropathy were used, and inverse variance weighted analysis was used as the primary analytical method, complemented by results from weighted median, MR-Egger regression, simple model, and median model approaches. Sensitivity analysis was used to test the reliability of the MR analysis results. ResultsIn the inverse variance weighted method, stem cell factor (OR=1.28, 95%CI 1.04 to 1.58, P=0.020) and interferon-γ (OR=1.36, 95%CI 1.10 to 1.70, P=0.005) were positively correlated with diabetic nephropathy, and diabetic nephropathy was positively correlated with interferon-inducible protein 10 (OR=0.90, 95%CI 0.83 to 0.98, P=0.012) were negatively correlated with diabetic nephropathy. Sensitivity analysis showed that MR analysis was reliable. ConclusionStem cell factors and interferon-γ are associated with an increased risk of developing diabetic nephropathy, and diabetic nephropathy decreases the expression of interferon-inducible protein 10 in vivo. Our results demonstrate a potential causal relationship between inflammatory factors and the development of diabetic nephropathy. This finding is of clinical significance for the pre-diagnosis and treatment of diabetic nephropathy.