Abstract: Objective To explore the mechanism of miR-223-3p/SOX6 axis regulating inflammation and renal interstitial fibrosis in diabetic nephropathy (DN). Methods A DN model was established using db/db mice. Blood glucose and 24 h albumin excretion rate were measured. HK-2 cells were cultured with high glucose (HG). The expression of miR-223-3p in renal tissue/HK-2 cells was detected by PCR. The pathological changes of renal tissue was observed by H-E staining and Masson staining. The expression of inflammation factors, tumor necrosis factor (TNF)-α and interleukin (IL)-6, and fibronectin (FN) was detected by immunochemistry. Subsequently, miR-223-3p was over-expressed in cells and DN mice, and the inflammation and fibrosis of cell/tissue was detected. The targeting relationship between miR-223-3p and SOX6 was verified by dual luciferase reporter gene system and Western blot. Finally, miR-223-3p and SOX6 were co-overexpressed in DN mice to observe their effects on renal tissue. Results Compared with the normal control, down-regulated expression of miR-223-3p was detected in DN modeling mice presented (P<0.05), and in HK-2 cells cultured with HG (P<0.05). MiR-223-3p over-expression alleviated the inflammation and fibrosis of cell/renal tissue (P<0.05). MiR-223-3p inhibited the expression of SOX6 (P<0.05), and SOX6 was highly expressed in DN mice (P<0.05). Overexpression of SOX6 reversed the alleviating effect of miR-223-3p on renal inflammation and fibrosis in DN mice (P<0.05). Conclusions MiR-223-3p can alleviate renal inflammation and interstitial fibrosis in DN model, and prevent the progression of DN.