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Purpose. To explore the effect of Shenkang injection (SKI) combined with Jinshuibao for early diabetic nephropathy (DN) and its effect on the coagulation fibrinolysis system and urinary protein. Methods. 136 patients with early DN admitted to our hospital from March 2018 to October 2019 were divided into the observation group (n = 68) and the control group (n = 68) randomly. On the basis of the conventional treatment, the control group was treated with SKI, and the observation group was treated with SKI and Jinshuibao. Two weeks later, the therapeutic effects of the 2 groups were compared. The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and D-dimer (D-D) were observed and compared before and after the treatment. 24 hour urine total protein (24 h-UTP), urine albumin excretion rate (UAER), and urine β2 microglobulin (β2-MG) were measured and compared before and after the treatment. Adverse reactions in the two groups were recorded during the treatment. Results. The effective rate of the observation group after treatment was 92.65% higher than the control group 79.41%. the difference was statistically significant (P < 0.05). The levels of PT, APTT, TT, FIB, PAI-1, and D-D in the two groups after treatment were lower, and t-PA levels after treatment were higher than those before, and all of the above indicators were significantly changed in the observation group than in the control group. The difference was statistically significant (P < 0.05). The 24 h-UTP, UAER, and β2-MG in the two groups after treatment were lower than those before, and all of the above indicators were significantly changed in the observation group than in the control group. The difference was statistically significant (P < 0.05). There was no statistically significant difference during the treatment for 2 groups in terms of adverse reactions. The difference was statistically significant (P > 0.05). Conclusion. SKI combined with Jinshuibao has a significant effect in the treatment of early DN, which can reduce the risk of hyperfunction of coagulation and fibrinolysis system, further reduce the content of urine protein, and delay the process of DN. [ABSTRACT FROM AUTHOR]