Abstract: ob＜x＞jective: To explore the mechanism of miR-223-3p/SOX6 axis regulating inflammation and renal interstitial fibrosis in diabetic nephropathy(DN) . Methods: DN model was established by db/db mice. Blood glucose and 24-hour albumin excretion rate were measured.HK-2 cells were cultured with high glucose(HG) . The ex＜x＞pression of miR-223-3p in renal tissue/HK-2 cells was detected by PCR. The pathological status of renal tissue was observed bu HE staining and Masson staining. The ex＜x＞pression of inflammation factors (TNF-α and IL-6) and fibronectin (FN) was detected. Subsequetly，miR-223-3p was overexpressed in cells and DN mice, and the effects of cell/tissue inflammation and fibrosis was detected. The targeting relationship between miR-223-3p and SOX6 was verified by dual luciferase reporter gene system and Western blotting. Finally,miR-223-3p and SOX6 were co-overexpressed in DN mice to observed the effects on renal tissue. Results: Compared with normal control , the ex＜x＞pression of miR-223-3p was down regulated in DN model mice (P < 0.05) , and the ex＜x＞pression of miR-223-3p was also down regulated in HK-2 cells cultured with HG compared with NG(P < 0.05) . Overex＜x＞pression of miR-223-3p could alleviate inflammation and fibrosis of cell/ renal tissue (P < 0.05). miR-223-3p could inhibit the ex＜x＞pression of SOX6 (P < 0.05) , and the ex＜x＞pression level of SOX6 was high in DN mice (P < 0.05). Overex＜x＞pression of SOX6 could reverse the alleviating effect of miR-223-3p on renal inflammation and fibrosis in DN mice (P < 0.05) . Conclusion: MiR-223-3p can alleviate renal inflammation and interstitial fibrosis in DN model, and prevent the progression of DN