<p>This study was to investigate the mechanism of miR- 34c- 5p in alleviating kidney injury in diabetic nephropathy (DN) rats by targeting ROCK1 and MAPK/ERK signaling pathway. The rat model of DN was established and fasting blood glucose, 24-h proteinuria, blood urea nitrogen, and serum creatinine were measured to quantify kidney injury. Kidney tissue was dissected for H&amp;E and TUNEL staining. Renal injury factor KIM- 1 was measured by Western blot analysis. Retinal Muller cells (RMCs) were treated with high glucose and transfected. Cell viability was detected by CCK- 8 and apoptosis by flow cytometry. Inflammatory factors in DN rats and RMCs were analyzed by ELISA. The targeting effect of miR- 34c- 54p on ROCK1 was demonstrated by RNA pull-down and dual-luciferase reporter gene. Finally, ROCK1, p-MEK1/2, and p-ERK were assessed by Western blot. Elevating miR- 34c- 5p could inhibit DN kidney injury and high glucose–induced cell injury, and reduce inflammation in kidney tissue of DN rats and RMCs. miR- 34c- 5p targeted to regulate ROCK1 expression, and restoring ROCK1 abolished the therapeutic effect of elevating miR- 34c- 5p. Phosphorylated MEK and ERK were increased in DN rats and RMCs induced by high glucose. miR- 34c- 5p can inhibit kidney injury induced by DN by targeting ROCK1, and the MAPK/ERK pathway may represent the pathological mechanism of DN.</p>