Abstract： Objective： To observe the clinical effect of Yishen Xiezhuo Huoxue Prescription combined with Alprostadil on diabetic kidney disease (DKD). Methods： A total of 80 cases of DKD patients were selected as research objects and randomly divided into the control group and the observation group according to the random number table method，with 41 cases in each group. The control group was given routine treatment， and the observation group was additionally treated with Yishen Xiezhuo Huoxue Prescription combined with Alprostadil based on the treatment of the control group. Both groups were treated for 8 weeks. The clinical effects were compared between the two groups； the hemorheology indexes and the levels of matrix metalloproteinase- 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP- 1) in serum were compared before and after treatment between the two groups. Results： After treatment， the levels of 24- hour urinary protein quantitation (24 hPRO)， microalbuminuria (mAIb)， β2- microglobulin (β2-MG)，and cystatin C (CysC) in the two groups were decreased (P＜0.05)，and the above levels in the observation group were lower than those in the control group (P＜0.05). After treatment，the levels of whole blood high-shear viscosity (ηbH)，whole blood low-shear viscosity (ηbL)，plasma viscosity (ηp) and red blood cell aggregation indexes (AI) in the two groups were decreased (P＜0.05)，and the above levels in the observation group were lower than those in the control group (P＜0.05). After treatment， MMP- 9 and MMP- 9/TIMP- 1 in the two groups were increased (P＜0.05)，and TIMP- 1 was decreased (P＜0.05)；MMP-9 and MMP-9/TIMP-1 in serum in the observation group were higher than those in the control group (P＜0.05)， and TIMP- 1 was lower than that in the control group (P＜0.05). Conclusion： Yishen Xiezhuo Huoxue Prescription combined with Alprostadil has significant effects on reducing proteinuria and protecting kidney function of DKD patients，and its clinical effect is better than that of simple western medicine. The mechanism may be related to its ability to effectively regulate the expressions of MMP-9 and TIMP-1 in DKD patients，improve their hemorheology and reduce blood hyperviscosity.