Abstract: To investigate the effects and mechanism of andrographolide(Andro)on type II diabetic nephropathy in Lepr^db/dbmice, levels of urinary protein, serum creatinine and blood urea nitrogen after 24 h of Andro(1 mg/kg, ip)treatment on Lepr^db/db mice were measured by kit. The changes on renal pathology and sugar levels in diabetic mice treated by Andro were observed by HE staining and PAS staining. The expression of fibronectin(FN)and NOX-4 protein were analyzed by immunofluorescence. Results showed that levels of urinary protein, serum creatinine and blood urea nitrogenin Lepr^{db / db} mice after Andro treatment for 24 h were significantly lower than those of the control group. Kidney pathologic change was inhibited, and FN and NOX-4 expression were markedly decrease in the Andro group. In conclusion, Andro can significantly reduce the diabetic nephropathy in Lepr^db/db mice with spontaneous type II diabetes mellitus.