In this investigation, we revealed that LM49 can effectively ameliorate renal fibrosis and filtration function in kidneys with unilateral ureteral obstruction (UUO)‐ and folic acid (FA)‐induced fibrosis, which is related to the suppression of HMGB1‐induced inflammation and TECs necrosis. The gene discussed is HMGB1; the disease is renal fibrosis.