In the results, renal fibrosis characterized by significantly elevated expression levels of Col I, FN, and α-SMA was detected in the model group, whereas mangiferin treatment significantly reversed the elevated protein expressions of Col I, FN, and α-SMA in the diabetic mice, indicating a remarkable effect of mangiferin on renal fibrosis of DN mice. This evidence concerns the gene ACTA1 and liver dysplastic nodule.