Objective: To observe the effect of asiatic acid (AA) on renal function and macrophage surface activation markers in diabetic nephropathy (DN) rats. Methods: Fifty rats were selected, 40 of them were fed with high-fat diet and intraperitoneal injection of streptozotocin (STZ) to make DN model, which was randomly divided into a DN group, a low, a medium, a high dose AA group (LD, MD, HD group). The remaining 10 healthy rats were a control (NC) group. The 3 dose groups were given 10, 20, 40 mg/kg AA daily, and the DN and the NC groups were intragastrically administered with normal saline daily, the rats were sacrificed after 8 weeks. The renal function indexes were compared. The blood routine and liver function indicators were detected in the 3 dose groups. The right kidney was taken for gross observation and histopathological examination was performed. The number of CD68 positive cells in glomeruli and renal interstitium, the macrophage M1 activation markers [inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α)] and M2 activation markers [arginase-1 (Arg-1), mannose receptor (MR)] expressions in renal tissues were compared. Results: SCr, BUN, UA and 24 h total urinary protein levels were as follows: NC group, HD group, MD group, LD group, DN group, and the difference between each group was statistically significant (P<0.05). Gross right kidney observation showed that the volume of rats in the ND group was significantly higher than that in NC group, and the dose in group 3 was lower than that in the DN group. The blood routine and liver function indexes of the rats in the 3 dose groups were in the normal range. Pathological observation of PAS staining showed that the glomeruli, renal tubules and renal interstitial were normal in the NC group, glomerular atrophy, thickening of the basement membrane and increased mesangial matrix in the DN group, while the above pathological changes were gradually alleviated in the 3 dose group, and the HD group was the most obvious. The number of glomerular and renal interstitial CD68 positive cells and the relative protein expressions of iNOS and TNF-α in renal were as follows: NC group, HD group, MD group, LD group, DN group, and the difference between the 2 groups was statistically significant (P<0.05). The relative expressions of Arg-1 and MR proteins in renal were as follows: NC group, DN group, LD group, MD group, HD group, and the difference between the two groups was statistically significant (P<0.05). Conclusion: AA can effectively improve renal function and reduce renal tissue damage in DN rats, with 40 mg/kg AA being the best. It may be related to inhibition of M1 type macrophage activation and enhancement of M2 type macrophage activation.